B cells: Types and Functions

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.

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

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.