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B cells: Types and Functions

B lymphocytes Lymphocytes Lymphocytes are heterogeneous WBCs involved in immune response. Lymphocytes develop from the bone marrow, starting from hematopoietic stem cells (HSCs) and progressing to common lymphoid progenitors (CLPs). B and T lymphocytes and natural killer (NK) cells arise from the lineage. Lymphocytes: Histology, also known as B cells, are important components of the adaptive immune system Immune system The body's defense mechanism against foreign organisms or substances and deviant native cells. It includes the humoral immune response and the cell-mediated response and consists of a complex of interrelated cellular, molecular, and genetic components. Primary Lymphatic Organs. In the bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types marrow, the hematopoietic stem cells Hematopoietic stem cells Progenitor cells from which all blood cells derived. They are found primarily in the bone marrow and also in small numbers in the peripheral blood. Bone Marrow: Composition and Hematopoiesis go through a series of steps to become mature naive B cells. The cells migrate to secondary lymphoid organs Lymphoid organs A system of organs and tissues that process and transport immune cells and lymph. Primary Lymphatic Organs for activation and further maturation. The process entails antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination stimulation, with or without the help of T cells T cells Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (t-lymphocytes, cytotoxic) and helper T-lymphocytes (t-lymphocytes, helper-inducer). They are formed when lymphocytes circulate through the thymus gland and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen. T cells: Types and Functions. The T-cell–independent activation generates a short-lived immune response (via plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products cells), and this is seen with antigens such as bacterial lipopolysaccharides Lipopolysaccharides Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: lipid a, core polysaccharide, and o-specific chains (o antigens). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal b-cell mitogens commonly used in laboratory immunology. Diarrheagenic E. coli. T-cell–dependent activation, on the other hand Hand The hand constitutes the distal part of the upper limb and provides the fine, precise movements needed in activities of daily living. It consists of 5 metacarpal bones and 14 phalanges, as well as numerous muscles innervated by the median and ulnar nerves. Hand: Anatomy, produces both plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products cells and memory cells Memory cells Cells that outlived a previous infection Adaptive Immune Response. Activated B cells Activated B cells Humoral Adaptive Immunity then proliferate in the germinal centers, but not all become effector B cells. Through somatic hypermutation, B cells undergo additional mechanisms to increase the affinity of the antibody to the antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination. Only those with high-affinity B-cell receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors subsequently advance for terminal differentiation. B cells then go through class switching (from IgM IgM A class of immunoglobulin bearing mu chains (immunoglobulin mu-chains). Igm can fix complement. The name comes from its high molecular weight and originally being called a macroglobulin. Immunoglobulins: Types and Functions to another class of Ig Ig X-linked Agammaglobulinemia) under the influence of cytokines Cytokines Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. Adaptive Immune Response. After class switching, the B cells become plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products cells (which produce antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions) or memory cells Memory cells Cells that outlived a previous infection Adaptive Immune Response (which mount a robust secondary immune response Secondary immune response Humoral Adaptive Immunity).

Last updated: 10 Mar, 2022

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

B-Cell Development

Definition

B (bursa-derived) lymphocytes Lymphocytes Lymphocytes are heterogeneous WBCs involved in immune response. Lymphocytes develop from the bone marrow, starting from hematopoietic stem cells (HSCs) and progressing to common lymphoid progenitors (CLPs). B and T lymphocytes and natural killer (NK) cells arise from the lineage. Lymphocytes: Histology, or B cells, are a type of lymphocyte that arises from the common lymphoid progenitor.

  • Involved in humoral adaptive immunity Humoral Adaptive Immunity Humoral adaptive immunity is an integral part of the adaptive immune system, which mounts a highly specific defense against pathogens but takes a longer time to respond (compared to the innate immune system). Humoral immunity is the arm of the immune system protecting the extracellular fluids of the lymphatics (lymph), interstitium, and circulatory system (plasma) from microbial contamination mediated through soluble molecules. Humoral Adaptive Immunity
  • Functions: 
    • B cells differentiate into plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products cells → produce antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions (which prevent infection by inhibiting microbes from attaching to target cells) 
    • B cells differentiate into memory cells Memory cells Cells that outlived a previous infection Adaptive Immune Response → activated against reinfection

Development

  • Begins transiently in the fetal liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy prenatally and continues in the bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types marrow throughout life
  • In the bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types marrow: hematopoietic stem cells Hematopoietic stem cells Progenitor cells from which all blood cells derived. They are found primarily in the bone marrow and also in small numbers in the peripheral blood. Bone Marrow: Composition and Hematopoiesis (HSCs) → common lymphoid progenitor (CLP)
  • In order to produce a functional mature B cell Mature B cell Lymphocytes: Histology from the CLP:
    • Cell-surface Ig Ig X-linked Agammaglobulinemia molecule (a part of the B-cell receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors ( BCR BCR Lymphocytes: Histology)) has to be expressed.
    • Germ-line DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure does not have the complete genes Genes A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. DNA Types and Structure encoding a complete Ig Ig X-linked Agammaglobulinemia.
    • Gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics rearrangements (uniting different gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics segments) within B cells are needed to assemble the Ig Ig X-linked Agammaglobulinemia molecule.
    • This process also produces a repertoire of diverse B cells; these, in effect, create protection against different kinds of infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease.
  • Cell-surface ( Ig Ig X-linked Agammaglobulinemia) molecule:
    • Has heavy chains Heavy chains The largest of polypeptide chains comprising immunoglobulins. They contain 450 to 600 amino acid residues per chain, and have molecular weights of 51-72 kda. Immunoglobulins: Types and Functions (μ, δ, γ, α, or ε) disulfide-linked to light chains Light chains Polypeptide chains, consisting of 211 to 217 amino acid residues and having a molecular weight of approximately 22 kda. There are two major types of light chains, kappa and lambda. Two ig light chains and two ig heavy chains (immunoglobulin heavy chains) make one immunoglobulin molecule. Immunoglobulins: Types and Functions (κ or λ)
    • Heavy-chain genes Heavy-chain genes Genes and gene segments encoding the immunoglobulin heavy chains. Gene segments of the heavy chain genes are symbolized V (variable), d (diversity), j (joining), and c (constant). Immunoglobulins: Types and Functions (found within a single gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics locus Locus Specific regions that are mapped within a genome. Genetic loci are usually identified with a shorthand notation that indicates the chromosome number and the position of a specific band along the P or Q arm of the chromosome where they are found. For example the locus 6p21 is found within band 21 of the P-arm of chromosome 6. Many well known genetic loci are also known by common names that are associated with a genetic function or hereditary disease. Basic Terms of Genetics, Ig Ig X-linked Agammaglobulinemia heavy chain (IGH)), are assembled from 4 gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics segments:
      • Variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables region (V)
      • Diversity segment (D)
      • Joining region (J)
      • Constant region Constant region The domains of the immunoglobulin molecules that are invariable in their amino acid sequence within any class or subclass of immunoglobulin. They confer biological as well as structural functions to immunoglobulins. One each on both the light chains and the heavy chains comprises the c-terminus half of the immunoglobulin fab fragment and two or three of them make up the rest of the heavy chains (all of the immunoglobulin Fc fragment). Immunoglobulins: Types and Functions (C)
    • The light-chain genes Genes A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. DNA Types and Structure (found as 2 separate gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics loci: the κ locus Locus Specific regions that are mapped within a genome. Genetic loci are usually identified with a shorthand notation that indicates the chromosome number and the position of a specific band along the P or Q arm of the chromosome where they are found. For example the locus 6p21 is found within band 21 of the P-arm of chromosome 6. Many well known genetic loci are also known by common names that are associated with a genetic function or hereditary disease. Basic Terms of Genetics [IGK] and the λ locus Locus Specific regions that are mapped within a genome. Genetic loci are usually identified with a shorthand notation that indicates the chromosome number and the position of a specific band along the P or Q arm of the chromosome where they are found. For example the locus 6p21 is found within band 21 of the P-arm of chromosome 6. Many well known genetic loci are also known by common names that are associated with a genetic function or hereditary disease. Basic Terms of Genetics [IGL]) come from 3 gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics segments:
      • Variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables region (V)
      • Joining region (J) 
      • Constant region Constant region The domains of the immunoglobulin molecules that are invariable in their amino acid sequence within any class or subclass of immunoglobulin. They confer biological as well as structural functions to immunoglobulins. One each on both the light chains and the heavy chains comprises the c-terminus half of the immunoglobulin fab fragment and two or three of them make up the rest of the heavy chains (all of the immunoglobulin Fc fragment). Immunoglobulins: Types and Functions (C)
B-cell receptor (bcr)

The B-cell receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors ( BCR BCR Lymphocytes: Histology) consists of the Ig Ig X-linked Agammaglobulinemia molecule and the signaling molecule:
Ig Ig X-linked Agammaglobulinemia contains 2 identical heavy chains Heavy chains The largest of polypeptide chains comprising immunoglobulins. They contain 450 to 600 amino acid residues per chain, and have molecular weights of 51-72 kda. Immunoglobulins: Types and Functions and 2 identical light chains Light chains Polypeptide chains, consisting of 211 to 217 amino acid residues and having a molecular weight of approximately 22 kda. There are two major types of light chains, kappa and lambda. Two ig light chains and two ig heavy chains (immunoglobulin heavy chains) make one immunoglobulin molecule. Immunoglobulins: Types and Functions linked by a disulfide bridge. The membrane-bound Ig Ig X-linked Agammaglobulinemia is anchored to the cell surface.

Image:“Figure 42 02 06” by OpenStax. License: CC BY 4.0

Stages

To reach functionality, the B cell goes through stages in the bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types marrow and the secondary lymphoid organs Lymphoid organs A system of organs and tissues that process and transport immune cells and lymph. Primary Lymphatic Organs:

  • In the initial stages occurring in the bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types marrow, the aim is to build the receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors (requiring no antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination). 
  • When released to the secondary lymphoid organs Lymphoid organs A system of organs and tissues that process and transport immune cells and lymph. Primary Lymphatic Organs, an antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination (with or without T-cell help) will activate the B cell to continue the maturation process.
Table: Stages of B-cell development
Maturation stage Ig Ig X-linked Agammaglobulinemia genes Genes A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. DNA Types and Structure B-cell receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors ( BCR BCR Lymphocytes: Histology) Associated events
Antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination-independent
Pre-pro-B cell Pre-pro-B cell Lymphocytes: Histology Germ-line DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure None No heavy- or light-chain expression
Pro-B cell Pro-B cell Lymphocytes: Histology IGH D-J rearranged None Starts to express CD19, CD34, and HLA-DR (class II histocompatibility antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination)
Pre-B cell IGH V-D-J rearranged Pre- BCR BCR Lymphocytes: Histology is formed:
  • Heavy chain present
  • Surrogate light chain present
Other markers appear (CD79, CD10, CD20, CD40 CD40 Members of the tumor necrosis factor receptor superfamily with specificity for CD40 ligand. They are found on mature B-lymphocytes, some epithelial cells; and lymphoid dendritic cells. Evidence suggests that CD40-dependent activation of B-cells is important for generation of memory B-cells within the germinal centers. Mutations in the CD40 antigen gene result in hyper-igm immunodeficiency syndrome, type 3. Signaling of the receptor occurs through its association with tnf receptor-associated factors. Hyper-IgM Syndrome, and terminal deoxynucleotidyl transferase Terminal deoxynucleotidyl transferase A non-template-directed DNA polymerase normally found in vertebrate thymus and bone marrow. It catalyzes the elongation of oligo- or polydeoxynucleotide chains and is widely used as a tool in the differential diagnosis of acute leukemias in man. Acute Lymphoblastic Leukemia among them).
Immature B cell Immature B cell Lymphocytes: Histology
  • IGH V-D-J rearranged
  • Light-chain V-J rearranged
Mature BCR BCR Lymphocytes: Histology ( IgM IgM A class of immunoglobulin bearing mu chains (immunoglobulin mu-chains). Igm can fix complement. The name comes from its high molecular weight and originally being called a macroglobulin. Immunoglobulins: Types and Functions molecule) HLA-DR, CD19, CD20, and CD40 CD40 Members of the tumor necrosis factor receptor superfamily with specificity for CD40 ligand. They are found on mature B-lymphocytes, some epithelial cells; and lymphoid dendritic cells. Evidence suggests that CD40-dependent activation of B-cells is important for generation of memory B-cells within the germinal centers. Mutations in the CD40 antigen gene result in hyper-igm immunodeficiency syndrome, type 3. Signaling of the receptor occurs through its association with tnf receptor-associated factors. Hyper-IgM Syndrome expression continues, but not the other markers (e.g., CD10, CD34, and terminal deoxynucleotidyl transferase Terminal deoxynucleotidyl transferase A non-template-directed DNA polymerase normally found in vertebrate thymus and bone marrow. It catalyzes the elongation of oligo- or polydeoxynucleotide chains and is widely used as a tool in the differential diagnosis of acute leukemias in man. Acute Lymphoblastic Leukemia).
Mature B cell Mature B cell Lymphocytes: Histology (naive)
  • IGH V-D-J rearranged
  • Light chain V-J rearranged
With mature BCR BCR Lymphocytes: Histology ( IgM IgM A class of immunoglobulin bearing mu chains (immunoglobulin mu-chains). Igm can fix complement. The name comes from its high molecular weight and originally being called a macroglobulin. Immunoglobulins: Types and Functions) → exit bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types marrow All express CD19 and CD20.
Antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination-dependent
Mature B cell Mature B cell Lymphocytes: Histology (in secondary lymphoid tissues) Mature BCR BCR Lymphocytes: Histology (expresses IgM IgM A class of immunoglobulin bearing mu chains (immunoglobulin mu-chains). Igm can fix complement. The name comes from its high molecular weight and originally being called a macroglobulin. Immunoglobulins: Types and Functions and IgD IgD An immunoglobulin which accounts for less than 1% of plasma immunoglobulin. It is found on the membrane of many circulating B lymphocytes. Immunoglobulins: Types and Functions once within the secondary lymphoid tissues) Cells can rest or B-cell activation can occur: B cells interact with exogenous antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination and/or T helper cells.
Activated B cell Activated B cell Lymphocytes: Histology Class switching Once activated, can switch to IgE IgE An immunoglobulin associated with mast cells. Overexpression has been associated with allergic hypersensitivity. Immunoglobulins: Types and Functions, IgG IgG The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of igg, for example, igg1, igg2a, and igg2b. Hypersensitivity Pneumonitis, IgA IgA Represents 15-20% of the human serum immunoglobulins, mostly as the 4-chain polymer in humans or dimer in other mammals. Secretory iga is the main immunoglobulin in secretions. Immunoglobulins: Types and Functions, or remain as IgM IgM A class of immunoglobulin bearing mu chains (immunoglobulin mu-chains). Igm can fix complement. The name comes from its high molecular weight and originally being called a macroglobulin. Immunoglobulins: Types and Functions
Memory Memory Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. Psychiatric Assessment B cell
  • Activated B cell Activated B cell Lymphocytes: Histology → some become memory Memory Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. Psychiatric Assessment B cells
  • Circulate, ready to react to antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination stimulation and generate plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products cells
Plasma cell Plasma cell Specialized forms of antibody-producing B-lymphocytes. They synthesize and secrete immunoglobulin. They are found only in lymphoid organs and at sites of immune responses and normally do not circulate in the blood or lymph. Lymphocytes: Histology
  • Activated B cell Activated B cell Lymphocytes: Histology → some become plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products cells
  • Large cells secreting antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions fighting infection
  • Migrate to the bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types marrow
D: diversity segment
J: joining region
V: variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables region
Differentiation stages of the b cell

Differentiation stages of the B cell:
In antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination-independent stages, B-cell production starts with the hematopoietic stem cell (HSC), which becomes a common lymphoid progenitor (CLP) and then a pre-pro-B cell Pre-pro-B cell Lymphocytes: Histology or B-progenitor cell. The next steps include gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics rearrangement to assemble the Ig Ig X-linked Agammaglobulinemia molecule. Ig Ig X-linked Agammaglobulinemia heavy chains Heavy chains The largest of polypeptide chains comprising immunoglobulins. They contain 450 to 600 amino acid residues per chain, and have molecular weights of 51-72 kda. Immunoglobulins: Types and Functions start with rearrangement of diversity and joining segments to form the pro-B cell Pro-B cell Lymphocytes: Histology. In the next step (pre-B cell), Ig Ig X-linked Agammaglobulinemia heavy-chain recombination Recombination Production of new arrangements of DNA by various mechanisms such as assortment and segregation, crossing over; gene conversion; genetic transformation; genetic conjugation; genetic transduction; or mixed infection of viruses. Virology ( variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables, diversity, joining) is completed and the pre-B-cell receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors is formed. Light-chain (kappa (κ) or lambda (λ)) rearrangement occurs, resulting in the expression of a complete IgM IgM A class of immunoglobulin bearing mu chains (immunoglobulin mu-chains). Igm can fix complement. The name comes from its high molecular weight and originally being called a macroglobulin. Immunoglobulins: Types and Functions-antibody molecule by an immature B cell Immature B cell Lymphocytes: Histology. Formation of the mature B cell Mature B cell Lymphocytes: Histology (naive) with both IgM IgM A class of immunoglobulin bearing mu chains (immunoglobulin mu-chains). Igm can fix complement. The name comes from its high molecular weight and originally being called a macroglobulin. Immunoglobulins: Types and Functions and IgD IgD An immunoglobulin which accounts for less than 1% of plasma immunoglobulin. It is found on the membrane of many circulating B lymphocytes. Immunoglobulins: Types and Functions follows.
Antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination-dependent stages take place in secondary lymphoid tissues. Once the mature B cell Mature B cell Lymphocytes: Histology produce IgM IgM A class of immunoglobulin bearing mu chains (immunoglobulin mu-chains). Igm can fix complement. The name comes from its high molecular weight and originally being called a macroglobulin. Immunoglobulins: Types and Functions and IgD IgD An immunoglobulin which accounts for less than 1% of plasma immunoglobulin. It is found on the membrane of many circulating B lymphocytes. Immunoglobulins: Types and Functions, a class switch can take place to make IgE IgE An immunoglobulin associated with mast cells. Overexpression has been associated with allergic hypersensitivity. Immunoglobulins: Types and Functions, IgG IgG The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of igg, for example, igg1, igg2a, and igg2b. Hypersensitivity Pneumonitis, and IgA IgA Represents 15-20% of the human serum immunoglobulins, mostly as the 4-chain polymer in humans or dimer in other mammals. Secretory iga is the main immunoglobulin in secretions. Immunoglobulins: Types and Functions. B cells are activated and become plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products cells or memory cells Memory cells Cells that outlived a previous infection Adaptive Immune Response.

Image by Lecturio. License: CC BY-NC-SA 4.0

B-Cell Activation

The B cell migrates from the bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types marrow to the secondary lymphoid organs Lymphoid organs A system of organs and tissues that process and transport immune cells and lymph. Primary Lymphatic Organs. This process takes a number of measures to produce a functional differentiated B cell: activation by an antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination, proliferation, affinity maturation Affinity maturation Humoral Adaptive Immunity, class switching, and differentiation (into plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products or memory Memory Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. Psychiatric Assessment cell).

Initial process of activation

  • Naive B cells migrate to secondary lymphoid organs Lymphoid organs A system of organs and tissues that process and transport immune cells and lymph. Primary Lymphatic Organs, primarily the lymph nodes Lymph Nodes They are oval or bean shaped bodies (1 – 30 mm in diameter) located along the lymphatic system. Lymphatic Drainage System: Anatomy and the spleen Spleen The spleen is the largest lymphoid organ in the body, located in the LUQ of the abdomen, superior to the left kidney and posterior to the stomach at the level of the 9th-11th ribs just below the diaphragm. The spleen is highly vascular and acts as an important blood filter, cleansing the blood of pathogens and damaged erythrocytes. Spleen: Anatomy.
    • In the lymph nodes Lymph Nodes They are oval or bean shaped bodies (1 – 30 mm in diameter) located along the lymphatic system. Lymphatic Drainage System: Anatomy:
      • B cells are in the cortex.
      • T cells T cells Lymphocytes responsible for cell-mediated immunity. Two types have been identified – cytotoxic (t-lymphocytes, cytotoxic) and helper T-lymphocytes (t-lymphocytes, helper-inducer). They are formed when lymphocytes circulate through the thymus gland and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen. T cells: Types and Functions are in the paracortex Paracortex Secondary Lymphatic Organs.
      • B-cell entry into the tissue is by binding to a specialized endothelium Endothelium A layer of epithelium that lines the heart, blood vessels (vascular endothelium), lymph vessels (lymphatic endothelium), and the serous cavities of the body. Arteries: Histology ( high endothelial venules High endothelial venules The point of entry into lymph nodes for most circulating lymphocytes. Secondary Lymphatic Organs ( HEVs HEVs The point of entry into lymph nodes for most circulating lymphocytes. Secondary Lymphatic Organs)).
    • Once in the secondary lymphoid organs Lymphoid organs A system of organs and tissues that process and transport immune cells and lymph. Primary Lymphatic Organs, surface IgM IgM A class of immunoglobulin bearing mu chains (immunoglobulin mu-chains). Igm can fix complement. The name comes from its high molecular weight and originally being called a macroglobulin. Immunoglobulins: Types and Functions and IgD IgD An immunoglobulin which accounts for less than 1% of plasma immunoglobulin. It is found on the membrane of many circulating B lymphocytes. Immunoglobulins: Types and Functions are expressed.
  • The B cells are resting cells that undergo apoptosis Apoptosis A regulated cell death mechanism characterized by distinctive morphologic changes in the nucleus and cytoplasm, including the endonucleolytic cleavage of genomic DNA, at regularly spaced, internucleosomal sites, I.e., DNA fragmentation. It is genetically-programmed and serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. Ischemic Cell Damage if not activated (by antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination).
  • Two signals are needed for activation of B cells:
    • Signal 1: binding of antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination to the BCR BCR Lymphocytes: Histology (the more BCRs cross-linked by the antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination, the stronger the signal)
    • Signal 2: 
      • Inflammatory sources or antigens present a threat to the host.
      • Without signal 2, B cells do not become activated (this prevents inadvertent activation by harmless antigens).
Histologic section of the lymph node showing the cortex, paracortex and the medulla

Histologic section of the lymph Lymph The interstitial fluid that is in the lymphatic system. Secondary Lymphatic Organs node showing the cortex, paracortex Paracortex Secondary Lymphatic Organs and the medulla

Image by Geoffrey Meyer, edited by Lecturio.
Structure and functional regions of a lymph node

Structure and functional regions of a lymph Lymph The interstitial fluid that is in the lymphatic system. Secondary Lymphatic Organs node: comprise a collagen Collagen A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin; connective tissue; and the organic substance of bones (bone and bones) and teeth (tooth). Connective Tissue: Histology-rich fibrous Fibrous Fibrocystic Change capsule Capsule An envelope of loose gel surrounding a bacterial cell which is associated with the virulence of pathogenic bacteria. Some capsules have a well-defined border, whereas others form a slime layer that trails off into the medium. Most capsules consist of relatively simple polysaccharides but there are some bacteria whose capsules are made of polypeptides. Bacteroides and an underlying subcapsular sinus Subcapsular sinus Secondary Lymphatic Organs (SCS).
Cells are segregated into (1) the cortex (consisting of B cells, T follicular helper cells Follicular helper cells A specialized subpopulation of CD4+ T cells involved in formation of germinal center. Tfh cells are mostly located in secondary lymphoid organs, e.g., tonsil; spleen and lymph nodes. They are CD4 antigen; CD45 antigen; b-cell lymphoma 6 protein; cxcr5 receptors; icos inducible t-cell co-stimulator; and pd1 receptor positive. T cells: Types and Functions, and follicular dendritic cells Follicular dendritic cells Non-hematopoietic cells, with extensive dendritic processes, found in the primary and secondary follicles of lymphoid tissue (the B cell zones). They are different from conventional dendritic cells associated with T-cells. They are derived from mesenchymal stem cells and are negative for class II mhc antigen and do not process or present antigen like the conventional dendritic cells do. Instead, follicular dendritic cells have fc receptors and C3b receptors that hold antigen in the form of antigen-antibody complexes on their surfaces for long periods for recognition by B-cells. MALT Lymphoma [FDCs] arranged in primary follicles Primary follicles Secondary Lymphatic Organs, in which B cells survey antigens presented on the FDC stromal network); and (2) the paracortex Paracortex Secondary Lymphatic Organs (accommodates T cells T cells Lymphocytes responsible for cell-mediated immunity. Two types have been identified – cytotoxic (t-lymphocytes, cytotoxic) and helper T-lymphocytes (t-lymphocytes, helper-inducer). They are formed when lymphocytes circulate through the thymus gland and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen. T cells: Types and Functions, dendritic cells Dendritic cells Specialized cells of the hematopoietic system that have branch-like extensions. They are found throughout the lymphatic system, and in non-lymphoid tissues such as skin and the epithelia of the intestinal, respiratory, and reproductive tracts. They trap and process antigens, and present them to T-cells, thereby stimulating cell-mediated immunity. They are different from the non-hematopoietic follicular dendritic cells, which have a similar morphology and immune system function, but with respect to humoral immunity (antibody production). Skin: Structure and Functions [DCs], and fibroblastic reticular cells [FRCs] which form stromal cell networks and reticular fibers).
The inner medulla is composed of lymphatic tissues (medullary cords) separated by medullary sinuses consisting of lymph Lymph The interstitial fluid that is in the lymphatic system. Secondary Lymphatic Organs.

Image: “The structure of the lymph Lymph The interstitial fluid that is in the lymphatic system. Secondary Lymphatic Organs node” by Colbeck, Ager, Gallimore and Jones. License: CC BY 4.0

Clonal selection

  • Antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination challenge: 
    • Interaction occurs only between the antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination and the B cell with the appropriate “fit” or best “match” (based on the specific BCR BCR Lymphocytes: Histology).
    • This is a form of positive selection, with the newly bound B cell activated to respond.
    • Once binding occurs, that B cell divides, forming a clone.
  • The selected clone will undergo clonal expansion Clonal Expansion Seborrheic Keratosis (or proliferation) with the help of T cells T cells Lymphocytes responsible for cell-mediated immunity. Two types have been identified – cytotoxic (t-lymphocytes, cytotoxic) and helper T-lymphocytes (t-lymphocytes, helper-inducer). They are formed when lymphocytes circulate through the thymus gland and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen. T cells: Types and Functions.

Types of activation

B-cell activation by antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination presentation Presentation The position or orientation of the fetus at near term or during obstetric labor, determined by its relation to the spine of the mother and the birth canal. The normal position is a vertical, cephalic presentation with the fetal vertex flexed on the neck. Normal and Abnormal Labor can have different paths:

  • T-cell-dependent:
    • Circulating antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination interacts with the BCR BCR Lymphocytes: Histology.
    • The antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination is endocytosed and degraded.
    • Then the peptide components are complexed with cell-surface MHC II molecules.
    • Role of T cells T cells Lymphocytes responsible for cell-mediated immunity. Two types have been identified – cytotoxic (t-lymphocytes, cytotoxic) and helper T-lymphocytes (t-lymphocytes, helper-inducer). They are formed when lymphocytes circulate through the thymus gland and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen. T cells: Types and Functions:
      • T follicular helper (Tfh) cells are specialized CD4+ T helper cells previously activated by dendritic cells Dendritic cells Specialized cells of the hematopoietic system that have branch-like extensions. They are found throughout the lymphatic system, and in non-lymphoid tissues such as skin and the epithelia of the intestinal, respiratory, and reproductive tracts. They trap and process antigens, and present them to T-cells, thereby stimulating cell-mediated immunity. They are different from the non-hematopoietic follicular dendritic cells, which have a similar morphology and immune system function, but with respect to humoral immunity (antibody production). Skin: Structure and Functions (by presenting the same antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination).
      • The Tfh cells recognize and bind BIND Hyperbilirubinemia of the Newborn the antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination–MHC II complex.
      • The Tfh cells then express CD40 CD40 Members of the tumor necrosis factor receptor superfamily with specificity for CD40 ligand. They are found on mature B-lymphocytes, some epithelial cells; and lymphoid dendritic cells. Evidence suggests that CD40-dependent activation of B-cells is important for generation of memory B-cells within the germinal centers. Mutations in the CD40 antigen gene result in hyper-igm immunodeficiency syndrome, type 3. Signaling of the receptor occurs through its association with tnf receptor-associated factors. Hyper-IgM Syndrome ligand (CD40L), which binds B-cell CD40 CD40 Members of the tumor necrosis factor receptor superfamily with specificity for CD40 ligand. They are found on mature B-lymphocytes, some epithelial cells; and lymphoid dendritic cells. Evidence suggests that CD40-dependent activation of B-cells is important for generation of memory B-cells within the germinal centers. Mutations in the CD40 antigen gene result in hyper-igm immunodeficiency syndrome, type 3. Signaling of the receptor occurs through its association with tnf receptor-associated factors. Hyper-IgM Syndrome, leading to B-cell activation and proliferation.
    • Activated B cells Activated B cells Humoral Adaptive Immunity enter and proliferate in the germinal centers, where they continue the process, leading to differentiation.
    • An example of this is the 13-valent pneumococcal conjugate vaccine Vaccine Suspensions of killed or attenuated microorganisms (bacteria, viruses, fungi, protozoa), antigenic proteins, synthetic constructs, or other bio-molecular derivatives, administered for the prevention, amelioration, or treatment of infectious and other diseases. Vaccination (PCV13):
      • The polysaccharide–protein conjugate induces a T-cell–dependent immune response.
      • Forms both pneumococcal serotype ( PS PS Invasive Mechanical Ventilation)–specific antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions and memory Memory Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. Psychiatric Assessment B cells, creating immunologic memory Memory Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. Psychiatric Assessment.
  • T-cell-independent:
    • B-cell activation does not always need the help of T cells T cells Lymphocytes responsible for cell-mediated immunity. Two types have been identified – cytotoxic (t-lymphocytes, cytotoxic) and helper T-lymphocytes (t-lymphocytes, helper-inducer). They are formed when lymphocytes circulate through the thymus gland and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen. T cells: Types and Functions.
    • Some antigens, such as the polysaccharides Polysaccharides Basics of Carbohydrates of a bacterial cell, can directly stimulate B cells and bind BIND Hyperbilirubinemia of the Newborn many IgM IgM A class of immunoglobulin bearing mu chains (immunoglobulin mu-chains). Igm can fix complement. The name comes from its high molecular weight and originally being called a macroglobulin. Immunoglobulins: Types and Functions receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors to achieve a strong signal 1.
    • Signal 2 can be complement C3b Complement C3b The larger fragment generated from the cleavage of complement C3 by C3 convertase. It is a constituent of the alternative pathway C3 convertase (c3bbb), and complement C5 convertases in both the classical (c4b2a3b) and the alternative (c3bbb3b) pathway. C3b participates in immune adherence reaction and enhances phagocytosis. It can be inactivated (ic3b) or cleaved by various proteases to yield fragments such as complement C3c; complement C3d; C3e; C3f; and C3g. C3 Deficiency derivatives attached to the bacterial cell or pathogen-associated molecular patterns Pathogen-Associated Molecular Patterns Sepsis and Septic Shock.
    • Bypassing T-cell help, these responses are short-lived, generated mostly by IgM IgM A class of immunoglobulin bearing mu chains (immunoglobulin mu-chains). Igm can fix complement. The name comes from its high molecular weight and originally being called a macroglobulin. Immunoglobulins: Types and Functions production (limited class switching and no memory cells Memory cells Cells that outlived a previous infection Adaptive Immune Response).
    • An example is the pneumococcal polysaccharide vaccine Vaccine Suspensions of killed or attenuated microorganisms (bacteria, viruses, fungi, protozoa), antigenic proteins, synthetic constructs, or other bio-molecular derivatives, administered for the prevention, amelioration, or treatment of infectious and other diseases. Vaccination 23 (PPSV23):
      • Carries surface polysaccharides Polysaccharides Basics of Carbohydrates of 23 serotypes of Streptococcus Streptococcus Streptococcus is one of the two medically important genera of gram-positive cocci, the other being Staphylococcus. Streptococci are identified as different species on blood agar on the basis of their hemolytic pattern and sensitivity to optochin and bacitracin. There are many pathogenic species of streptococci, including S. pyogenes, S. agalactiae, S. pneumoniae, and the viridans streptococci. Streptococcus pneumoniae
      • Signal 1 is the polysaccharide, and signal 2 is the adjuvant Adjuvant Substances that augment, stimulate, activate, potentiate, or modulate the immune response at either the cellular or humoral level. The classical agents (freund’s adjuvant, bcg, corynebacterium parvum, et al.) contain bacterial antigens. Some are endogenous (e.g., histamine, interferon, transfer factor, tuftsin, interleukin-1). Their mode of action is either non-specific, resulting in increased immune responsiveness to a wide variety of antigens, or antigen-specific, i.e., affecting a restricted type of immune response to a narrow group of antigens. The therapeutic efficacy of many biological response modifiers is related to their antigen-specific immunoadjuvanticity. Vaccination (no peptides/protein to be recognized by Th cells).
      • With the 2 signals, B-cell activation and proliferation take place independently of T cells T cells Lymphocytes responsible for cell-mediated immunity. Two types have been identified – cytotoxic (t-lymphocytes, cytotoxic) and helper T-lymphocytes (t-lymphocytes, helper-inducer). They are formed when lymphocytes circulate through the thymus gland and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen. T cells: Types and Functions.
T- and b-cell binding

B-cell activation (T-cell-dependent):
Circulating antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination interacts with the BCR BCR Lymphocytes: Histology of the B cell. The antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination is endocytosed and degraded and the peptide components are complexed with cell surface MHC II molecules. T follicular helper (Tfh) cells (specialized CD4+ T helper cells) recognize and bind BIND Hyperbilirubinemia of the Newborn the antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination–MHC II complex. Cytokines Cytokines Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. Adaptive Immune Response are released by the Tfh cells, leading to B-cell activation and proliferation. Activated B cells Activated B cells Humoral Adaptive Immunity enter the germinal centers, where they continue the process, leading to differentiation.

Image: “T and B cell binding” by OpenStax College. License: CC BY 3.0

B-Cell Maturation and Differentiation

Affinity maturation Affinity maturation Humoral Adaptive Immunity

  • While the B cell has been activated, processes in the dark zone of the germinal center take place to further “fine-tune” the antibody affinity to the antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination.
  •   Affinity maturation Affinity maturation Humoral Adaptive Immunity is the mechanism by which B cells, after repeated stimulation, increase their affinity to a specific antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination presented to them.
  • Increased affinity is facilitated by somatic hypermutation (SHM):
    • A programmed mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations involving the variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables regions of Ig Ig X-linked Agammaglobulinemia heavy- and light-chain genes Genes A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. DNA Types and Structure, occurring after antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination-dependent activation
    • Driven by DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure-modifying enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes
      • Activation-induced cytidine deaminase (AID) 
      • Uracil Uracil One of four nucleotide bases in the nucleic acid RNA. Nucleic Acids nucleoside glycosylase (UNG) 
    • Produces BCR BCR Lymphocytes: Histology with enhanced ability to recognize and bind BIND Hyperbilirubinemia of the Newborn antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination
  • Selection:
    • After mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations, B cells with high-affinity BCRs now move to the light zone and access the antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination presented by follicular dendritic cells Follicular dendritic cells Non-hematopoietic cells, with extensive dendritic processes, found in the primary and secondary follicles of lymphoid tissue (the B cell zones). They are different from conventional dendritic cells associated with T-cells. They are derived from mesenchymal stem cells and are negative for class II mhc antigen and do not process or present antigen like the conventional dendritic cells do. Instead, follicular dendritic cells have fc receptors and C3b receptors that hold antigen in the form of antigen-antibody complexes on their surfaces for long periods for recognition by B-cells. MALT Lymphoma (FDCs). 
      • High affinity with the antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination → the more likely they are selected to present to and receive survival signals from Tfh cells
      • B cells with less affinity will not receive survival signals and will die by apoptosis Apoptosis A regulated cell death mechanism characterized by distinctive morphologic changes in the nucleus and cytoplasm, including the endonucleolytic cleavage of genomic DNA, at regularly spaced, internucleosomal sites, I.e., DNA fragmentation. It is genetically-programmed and serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. Ischemic Cell Damage.
  • This process not only allows diversity, but also permits only the most optimized B cells to survive and differentiate.

Class-switch recombination Recombination Production of new arrangements of DNA by various mechanisms such as assortment and segregation, crossing over; gene conversion; genetic transformation; genetic conjugation; genetic transduction; or mixed infection of viruses. Virology (CSR)

  • The surviving B cells (with high affinity to antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination) next undergo class switching, a step that also requires AID.
    • The constant region Constant region The domains of the immunoglobulin molecules that are invariable in their amino acid sequence within any class or subclass of immunoglobulin. They confer biological as well as structural functions to immunoglobulins. One each on both the light chains and the heavy chains comprises the c-terminus half of the immunoglobulin fab fragment and two or three of them make up the rest of the heavy chains (all of the immunoglobulin Fc fragment). Immunoglobulins: Types and Functions of the heavy chain can change the μ segment to one of the other heavy-chain segments (γ, ε, or α). 
    • The heavy-chain makeup determines the Ig Ig X-linked Agammaglobulinemia class: 
      • μ: IgM IgM A class of immunoglobulin bearing mu chains (immunoglobulin mu-chains). Igm can fix complement. The name comes from its high molecular weight and originally being called a macroglobulin. Immunoglobulins: Types and Functions
      • δ: IgD IgD An immunoglobulin which accounts for less than 1% of plasma immunoglobulin. It is found on the membrane of many circulating B lymphocytes. Immunoglobulins: Types and Functions
      • γ: IgG IgG The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of igg, for example, igg1, igg2a, and igg2b. Hypersensitivity Pneumonitis
      • α: IgA IgA Represents 15-20% of the human serum immunoglobulins, mostly as the 4-chain polymer in humans or dimer in other mammals. Secretory iga is the main immunoglobulin in secretions. Immunoglobulins: Types and Functions
      • ε: IgE IgE An immunoglobulin associated with mast cells. Overexpression has been associated with allergic hypersensitivity. Immunoglobulins: Types and Functions
    • Switching is influenced by cytokines Cytokines Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. Adaptive Immune Response.
      • TGF-β: preferentially switches to IgA IgA Represents 15-20% of the human serum immunoglobulins, mostly as the 4-chain polymer in humans or dimer in other mammals. Secretory iga is the main immunoglobulin in secretions. Immunoglobulins: Types and Functions
      • IL-4: IgE IgE An immunoglobulin associated with mast cells. Overexpression has been associated with allergic hypersensitivity. Immunoglobulins: Types and Functions
      • IFN IFN Interferon (IFN) is a cytokine with antiviral properties (it interferes with viral infections) and various roles in immunoregulation. The different types are type I IFN (IFN-ɑ and IFN-β), type II IFN (IFN-ɣ), and type III IFN (IFN-ƛ). Interferons-γ, IL-4: IgG IgG The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of igg, for example, igg1, igg2a, and igg2b. Hypersensitivity Pneumonitis
    • The constant region Constant region The domains of the immunoglobulin molecules that are invariable in their amino acid sequence within any class or subclass of immunoglobulin. They confer biological as well as structural functions to immunoglobulins. One each on both the light chains and the heavy chains comprises the c-terminus half of the immunoglobulin fab fragment and two or three of them make up the rest of the heavy chains (all of the immunoglobulin Fc fragment). Immunoglobulins: Types and Functions of Ig Ig X-linked Agammaglobulinemia heavy chain is changed, but the variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables region remains unchanged.
    • Since the variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables region is intact, specificity Specificity Specificity is the probability of correctly determining the absence of a condition. Immunoassays of the antibody does not change.
  • After class switching, B cells exit the germinal centers and terminally differentiate into plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products cells or memory cells Memory cells Cells that outlived a previous infection Adaptive Immune Response.
B-cell activation and maturation processes in the germinal center

B-cell activation and maturation processes taking place in the germinal center:
On activation, the B cell moves from the mantle zone and enters the germinal center. B-cell proliferation ( clonal expansion Clonal Expansion Seborrheic Keratosis) takes place and antibody affinity to the antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination is enhanced through the process of somatic hypermutation. Repeated cycles of proliferation and hypermutation fine-tune the B-cell receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors. However, not all B cells continue to differentiate, especially if the affinity is weak. Apoptosis Apoptosis A regulated cell death mechanism characterized by distinctive morphologic changes in the nucleus and cytoplasm, including the endonucleolytic cleavage of genomic DNA, at regularly spaced, internucleosomal sites, I.e., DNA fragmentation. It is genetically-programmed and serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. Ischemic Cell Damage follows if the antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination–antibody binding is not optimized. Those with strong affinity survive (selection), with the help of survival signals from follicular dendritic cells Follicular dendritic cells Non-hematopoietic cells, with extensive dendritic processes, found in the primary and secondary follicles of lymphoid tissue (the B cell zones). They are different from conventional dendritic cells associated with T-cells. They are derived from mesenchymal stem cells and are negative for class II mhc antigen and do not process or present antigen like the conventional dendritic cells do. Instead, follicular dendritic cells have fc receptors and C3b receptors that hold antigen in the form of antigen-antibody complexes on their surfaces for long periods for recognition by B-cells. MALT Lymphoma (DC) and T cells T cells Lymphocytes responsible for cell-mediated immunity. Two types have been identified – cytotoxic (t-lymphocytes, cytotoxic) and helper T-lymphocytes (t-lymphocytes, helper-inducer). They are formed when lymphocytes circulate through the thymus gland and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen. T cells: Types and Functions. These selected B cells move on to class switching and differentiation into plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products cells or memory cells Memory cells Cells that outlived a previous infection Adaptive Immune Response.

Image by Lecturio. License: CC BY-NC-SA 4.0
Haematoxylin and eosin stain of the germinal center of secondary lymphoid tissue

Germinal center: histology of the germinal center of a secondary lymphoid tissue
LZ: light zone
DZ: dark zone

Image: “Haematoxylin and eosin stain” by Petra Korać et al AL Amyloidosis. License: CC BY 4.0, cropped by Lecturio.

Plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products cells and memory cells Memory cells Cells that outlived a previous infection Adaptive Immune Response

  • Plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products cells: 
    • Large cells (up to 20 microns in diameter)
    • Produce antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions
    • Migrate to the bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types marrow
  • Memory cells Memory cells Cells that outlived a previous infection Adaptive Immune Response:
    • React to antigenic stimulation (in response to reinfection)
    • Generate plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products cells, which have high-affinity antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions in secondary immune responses
Summary of b-cell development to differentiation

Summary of B cell development to differentiation (from bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types marrow to secondary lymphoid organ):

B cell development:
In the bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types marrow, B cells develop into immature B cells, a process in which the B-cell receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors ( BCR BCR Lymphocytes: Histology) is assembled. Then the B cell migrates to the secondary lymphoid organs Lymphoid organs A system of organs and tissues that process and transport immune cells and lymph. Primary Lymphatic Organs, where activation occurs.

B cell activation B cell activation Humoral Adaptive Immunity:
The antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination binds the B cell with the “best match” BCR BCR Lymphocytes: Histology. One pathway of activation is T-cell–independent, whereby the activated B cell Activated B cell Lymphocytes: Histology is triggered to differentiate into a short-lived plasma cell Plasma cell Specialized forms of antibody-producing B-lymphocytes. They synthesize and secrete immunoglobulin. They are found only in lymphoid organs and at sites of immune responses and normally do not circulate in the blood or lymph. Lymphocytes: Histology (producing antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions) without the help of the T cell. In T-cell–dependent activation, the T cell recognizes the antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination–MHC II and triggers Triggers Hereditary Angioedema (C1 Esterase Inhibitor Deficiency) proliferation of the B cell in the germinal center of the lymphoid tissue.

Proliferation and maturation:
The process is followed by somatic hypermutation (SHM; a programmed mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations to further fine-tune the affinity of the antibody to the antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination). Repeated cycles of proliferation and hypermutation refine the BCR BCR Lymphocytes: Histology. Only those with the best affinity will be selected and survive; those with low affinity will undergo apoptosis Apoptosis A regulated cell death mechanism characterized by distinctive morphologic changes in the nucleus and cytoplasm, including the endonucleolytic cleavage of genomic DNA, at regularly spaced, internucleosomal sites, I.e., DNA fragmentation. It is genetically-programmed and serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. Ischemic Cell Damage. The surviving B cells then go through class-switch recombination Recombination Production of new arrangements of DNA by various mechanisms such as assortment and segregation, crossing over; gene conversion; genetic transformation; genetic conjugation; genetic transduction; or mixed infection of viruses. Virology (CSR), in which the heavy chain makeup is changed ( IgM IgM A class of immunoglobulin bearing mu chains (immunoglobulin mu-chains). Igm can fix complement. The name comes from its high molecular weight and originally being called a macroglobulin. Immunoglobulins: Types and Functions to other isotypes) with the help of cytokines Cytokines Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. Adaptive Immune Response.

Differentiation:
These B cells then differentiate into plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products cells and memory cells Memory cells Cells that outlived a previous infection Adaptive Immune Response, leaving the germinal center.

Image by Lecturio. License: CC BY-NC-SA 4.0

Antibody Diversity

From the initial B-cell production, many processes allow humans to produce different antibody molecules that are significantly more than the number of genes Genes A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. DNA Types and Structure in the genome Genome The complete genetic complement contained in the DNA of a set of chromosomes in a human. The length of the human genome is about 3 billion base pairs. Basic Terms of Genetics.

It is estimated that billions of antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions are generated, compared to about 30,000 genes Genes A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. DNA Types and Structure.

The immune system Immune system The body’s defense mechanism against foreign organisms or substances and deviant native cells. It includes the humoral immune response and the cell-mediated response and consists of a complex of interrelated cellular, molecular, and genetic components. Primary Lymphatic Organs has unique mechanisms to create antibody diversity, which include:

  • Having multiple V, D, J segments: 
    • As mentioned in the discussion of early B-cell development, the heavy chains Heavy chains The largest of polypeptide chains comprising immunoglobulins. They contain 450 to 600 amino acid residues per chain, and have molecular weights of 51-72 kda. Immunoglobulins: Types and Functions and light chains Light chains Polypeptide chains, consisting of 211 to 217 amino acid residues and having a molecular weight of approximately 22 kda. There are two major types of light chains, kappa and lambda. Two ig light chains and two ig heavy chains (immunoglobulin heavy chains) make one immunoglobulin molecule. Immunoglobulins: Types and Functions have multiple segments.
    • V, D, J, C for heavy chain
    • V, J, C for light chain
  • Rearrangements of the V, D, J segments:
    • DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure sequences (called recombination Recombination Production of new arrangements of DNA by various mechanisms such as assortment and segregation, crossing over; gene conversion; genetic transformation; genetic conjugation; genetic transduction; or mixed infection of viruses. Virology signal sequences (RSSs)) flank each gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics segment.
    • These sequences are recognition sites for the joining process.
    • Recombinase enzyme complex RAG1 RAG1 Immunoglobulins: Types and Functions and RAG2 RAG2 Immunoglobulins: Types and Functions ( recombination Recombination Production of new arrangements of DNA by various mechanisms such as assortment and segregation, crossing over; gene conversion; genetic transformation; genetic conjugation; genetic transduction; or mixed infection of viruses. Virology activating genes Genes A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. DNA Types and Structure 1 and 2) recognizes the RSS RSS Immunoglobulins: Types and Functions and catalyzes the joining process.
    • Deficiency in RAG1 RAG1 Immunoglobulins: Types and Functions or RAG2 RAG2 Immunoglobulins: Types and Functions can produce nonfunctional B cells. 
    • ***As previously mentioned in the earlier section, after the heavy chain segments, the light chain segments are also recombined.
  • Junctional diversity:
    • Joining of antibody gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics segments can be imprecise.
    • A number of nucleotides Nucleotides The monomeric units from which DNA or RNA polymers are constructed. They consist of a purine or pyrimidine base, a pentose sugar, and a phosphate group. Nucleic Acids can be removed and/or can be inserted from the ends of the recombining gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics segments.
  • Combinatorial diversity: Diversity is created by the random pairing of the heavy and light chains Light chains Polypeptide chains, consisting of 211 to 217 amino acid residues and having a molecular weight of approximately 22 kda. There are two major types of light chains, kappa and lambda. Two ig light chains and two ig heavy chains (immunoglobulin heavy chains) make one immunoglobulin molecule. Immunoglobulins: Types and Functions.
  • Somatic hypermutation: 
    • Point mutations occur with repeated antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination stimulation (from primary to secondary responses).
    • Increases affinity to antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination
    • Creates additional diversity to the antibody

Clinical Relevance

  • X-linked X-linked Genetic diseases that are linked to gene mutations on the X chromosome in humans or the X chromosome in other species. Included here are animal models of human X-linked diseases. Common Variable Immunodeficiency (CVID) agammaglobulinemia: results from mutations in the X- chromosome Chromosome In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. Basic Terms of Genetics gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics encoding for Bruton tyrosine Tyrosine A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine; thyroid hormones; and melanin. Synthesis of Nonessential Amino Acids kinase (BTK), which is essential for B-cell development and maturation. The disease is characterized by the absence of B cells, leading to recurrent infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease, primarily by encapsulated bacteria Encapsulated bacteria X-linked Agammaglobulinemia and viruses Viruses Minute infectious agents whose genomes are composed of DNA or RNA, but not both. They are characterized by a lack of independent metabolism and the inability to replicate outside living host cells. Virology, involving the lungs Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs: Anatomy, sinuses, and skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions, as well as the CNS. Treatment involves the administration of immune globulin.
  • Common variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables immunodeficiency Immunodeficiency Chédiak-Higashi Syndrome ( CVID CVID Common variable immune deficiency (CVID), also known as humoral immunodeficiency, is a disorder of the immune system characterized by reduced serum levels of immunoglobulins g, a, and m. Common Variable Immunodeficiency (CVID)): also known as humoral immunodeficiency Immunodeficiency Chédiak-Higashi Syndrome. Common variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables immunodeficiency Immunodeficiency Chédiak-Higashi Syndrome is a disorder of the immune system Immune system The body’s defense mechanism against foreign organisms or substances and deviant native cells. It includes the humoral immune response and the cell-mediated response and consists of a complex of interrelated cellular, molecular, and genetic components. Primary Lymphatic Organs characterized by reduced serum levels of IgG IgG The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of igg, for example, igg1, igg2a, and igg2b. Hypersensitivity Pneumonitis, IgA IgA Represents 15-20% of the human serum immunoglobulins, mostly as the 4-chain polymer in humans or dimer in other mammals. Secretory iga is the main immunoglobulin in secretions. Immunoglobulins: Types and Functions, and IgM IgM A class of immunoglobulin bearing mu chains (immunoglobulin mu-chains). Igm can fix complement. The name comes from its high molecular weight and originally being called a macroglobulin. Immunoglobulins: Types and Functions.  The underlying causes of CVID CVID Common variable immune deficiency (CVID), also known as humoral immunodeficiency, is a disorder of the immune system characterized by reduced serum levels of immunoglobulins g, a, and m. Common Variable Immunodeficiency (CVID) are largely unknown. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with this condition are prone to infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease in the GI tract and the upper and lower respiratory tracts. Common variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables immunodeficiency Immunodeficiency Chédiak-Higashi Syndrome is also associated with a higher risk of developing autoimmune disorders, granulomatous diseases Granulomatous diseases A defect of leukocyte function in which phagocytic cells ingest but fail to digest bacteria, resulting in recurring bacterial infections with granuloma formation. When chronic granulomatous disease is caused by mutations in the cybb gene, the condition is inherited in an X-linked recessive pattern. When chronic granulomatous disease is caused by cyba, ncf1, ncf2, or ncf4 gene mutations, the condition is inherited in an autosomal recessive pattern. Type IV Hypersensitivity Reaction, and malignancy Malignancy Hemothorax. The treatment is immune globulin replacement therapy.
  • Hyper IgM IgM A class of immunoglobulin bearing mu chains (immunoglobulin mu-chains). Igm can fix complement. The name comes from its high molecular weight and originally being called a macroglobulin. Immunoglobulins: Types and Functions syndrome: characterized by normal or elevated levels of IgM IgM A class of immunoglobulin bearing mu chains (immunoglobulin mu-chains). Igm can fix complement. The name comes from its high molecular weight and originally being called a macroglobulin. Immunoglobulins: Types and Functions with decreased or absent levels of other Igs Igs Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions. There are X-linked X-linked Genetic diseases that are linked to gene mutations on the X chromosome in humans or the X chromosome in other species. Included here are animal models of human X-linked diseases. Common Variable Immunodeficiency (CVID) and autosomal recessive Autosomal recessive Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal recessive diseases are only expressed when 2 copies of the recessive allele are inherited. Autosomal Recessive and Autosomal Dominant Inheritance types of hyper IgM IgM A class of immunoglobulin bearing mu chains (immunoglobulin mu-chains). Igm can fix complement. The name comes from its high molecular weight and originally being called a macroglobulin. Immunoglobulins: Types and Functions syndrome. The patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship present with recurrent sinopulmonary infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease, chronic diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea, and lymphoid hyperplasia Hyperplasia An increase in the number of cells in a tissue or organ without tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. Cellular Adaptation. The diagnosis is verified by genetic testing Genetic Testing Detection of a mutation; genotype; karyotype; or specific alleles associated with genetic traits, heritable diseases, or predisposition to a disease, or that may lead to the disease in descendants. It includes prenatal genetic testing. Myotonic Dystrophies. Treatment includes immune globulin replacement therapy and prophylactic antibiotics. Hematopoietic stem cell transplantation Hematopoietic stem cell transplantation Transfer of hematopoietic stem cells from bone marrow or blood between individuals within the same species (homologous transplantation) or transfer within the same individual (autologous transplantation). Hematopoietic stem cell transplantation has been used as an alternative to bone marrow transplantation in the treatment of a variety of neoplasms. Organ Transplantation is another option. 
  • IgA deficiency IgA deficiency A dysgammaglobulinemia characterized by a deficiency of immunoglobulin a. Selective IgA Deficiency: characterized by low levels of IgA IgA Represents 15-20% of the human serum immunoglobulins, mostly as the 4-chain polymer in humans or dimer in other mammals. Secretory iga is the main immunoglobulin in secretions. Immunoglobulins: Types and Functions, with normal IgG IgG The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of igg, for example, igg1, igg2a, and igg2b. Hypersensitivity Pneumonitis and IgM IgM A class of immunoglobulin bearing mu chains (immunoglobulin mu-chains). Igm can fix complement. The name comes from its high molecular weight and originally being called a macroglobulin. Immunoglobulins: Types and Functions levels. IgA deficiency IgA deficiency A dysgammaglobulinemia characterized by a deficiency of immunoglobulin a. Selective IgA Deficiency is the most common primary immunodeficiency Immunodeficiency Chédiak-Higashi Syndrome. Many patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship are asymptomatic; however, there is the potential for recurrent infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease as well as autoimmune disease. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship may be prone to anaphylactic transfusion reactions Transfusion reactions Transfusion-related complications occur during or after a blood product is given. These complications can be classified as immunologic, non-immunologic and acute, and delayed. Non-immunologic reactions are caused by the transmission of disease in blood products, and immunologic reactions are antigen-antibody-mediated. Transfusion Reactions because of the presence of IgA IgA Represents 15-20% of the human serum immunoglobulins, mostly as the 4-chain polymer in humans or dimer in other mammals. Secretory iga is the main immunoglobulin in secretions. Immunoglobulins: Types and Functions in blood products. Some of these cases eventually progress to CVID CVID Common variable immune deficiency (CVID), also known as humoral immunodeficiency, is a disorder of the immune system characterized by reduced serum levels of immunoglobulins g, a, and m. Common Variable Immunodeficiency (CVID).  Treatment involves prophylactic antibiotics and avoidance of blood products that contain IgA IgA Represents 15-20% of the human serum immunoglobulins, mostly as the 4-chain polymer in humans or dimer in other mammals. Secretory iga is the main immunoglobulin in secretions. Immunoglobulins: Types and Functions.

References

  1. Alberts, B., Johnson, A., Lewis, J., et al. (2002). The generation of antibody diversity. In: Molecular Biology of the Cell, 4th ed. New York: Garland Science. https://www.ncbi.nlm.nih.gov/books/NBK26860/
  2. Aster, J.C. (2021). Normal B and T lymphocyte development. UpToDate. Retrieved June 20, 2021, from https://www.uptodate.com/contents/normal-b-and-t-lymphocyte-development
  3. Fernandez, J. (2021). X-linked agammaglobulinemia. Merck Manual Professional Version. Retrieved June 20, 2021, from https://www.merckmanuals.com/professional/immunology-allergic-disorders/immunodeficiency-disorders/x-linked-agammaglobulinemia
  4. Fernandez, J. (2021). Common variable immunodeficiency (CVID). Merck Manual Professional Version. Retrieved June 20, 2021, from https://www.merckmanuals.com/professional/immunology-allergic-disorders/immunodeficiency-disorders/common-variable-immunodeficiency-cvid
  5. Fernandez, J. (2021). Hyper-IgM syndrome. Merck Manual Professional Version. Retrieved June 20, 2021, from https://www.merckmanuals.com/professional/immunology-allergic-disorders/immunodeficiency-disorders/hyper-igm-syndrome
  6. Fernandez, J. (2021). Selective IgA deficiency. Merck Manual Professional Version. Retrieved June 20, 2021, from https://www.merckmanuals.com/professional/immunology-allergic-disorders/immunodeficiency-disorders/selective-iga-deficiency
  7. Kipps, T.J. (2021). Functions of B lymphocytes and plasma cells in immunoglobulin production. In: Kaushansky, K., Prchal, J.T., Burns, L.J., Lichtman, M.A., Levi, M, Linch, D.C. (Eds.), Williams Hematology, 10th ed. McGraw-Hill. https://accessmedicine.mhmedical.com/content.aspx?bookid=2962&sectionid=252532543
  8. Levinson, W., Chin-Hong, P., Joyce, E.A., Nussbaum, J., Schwartz, B.(Eds.). (2020). Adaptive immunity: B cells & antibodies. In: Review of Medical Microbiology & Immunology: A Guide to Clinical Infectious Diseases, 16th ed. McGraw-Hill. https://accessmedicine.mhmedical.com/content.aspx?bookid=2867&sectionid=242768384
  9. Liew, P. (2012). The Longevity of the Humoral Immune Response: Survival of Long-lived Plasma Cells. Akademeia. 2. ea0116. 
  10. Riedel, S., Hobden, J.A., Miller, S., Morse, S.A., Mietzner, T.A., Detrick, B., Mitchell, T.G., Sakanari, J.A., Hotez, P, Mejia, R. (Eds.), (2019). Immunology. In: Jawetz, Melnick, & Adelberg’s Medical Microbiology, 28th ed. McGraw-Hill. https://accessmedicine.mhmedical.com/content.aspx?bookid=2629&sectionid=217769996
  11. Schroeder, H.W., Cavacini, L. (2010). Structure and function of immunoglobulins. J Allergy Clin Immunol 125(2 Suppl 2):S41–S52. https://pubmed.ncbi.nlm.nih.gov/20176268/
  12. Walter, J. (2021). Immunoglobulin genetics. UpToDate. Retrieved June 20, 2021, from https://www.uptodate.com/contents/immunoglobulin-genetics

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