Information about Immunoglobulin Class Switching

Immunoglobulin class switching (or isotype switching or Isotypic Commutation) is a biological mechanism that changes an antibody from one class to another, for example, from an isotype called IgM to an isotype called IgG. During this process, the constant region portion of the antibody heavy chain is changed, but the variable region of the heavy chain stays the same. Since the variable region does not change, class switching does not effect the antigens that are bound by the antibody. Instead, the antibody retains avidity for the same antigens, but can interact with different effector molecules.

Mechanism

Class switching occurs after activation of a mature B cell via its membrane-bound antibody molecule (or B cell receptor) to generate the different classes of antibody, all with the same variable domains as the original antibody generated in the immature B cell during the process of V(D)J recombination, but possessing distinct constant domains in their heavy chains.^[1]

Naïve mature B cells produce both IgM and IgD that have identical antigen binding regions. After activation by antigen, some B cells will class switch to produce IgG, IgA or IgE antibodies. During class switching, the constant region of the immunoglobulin heavy chain changes but the variable regions, and therefore antigen specificity, stay the same. This allows different daughter cells from the same activated B cell to produce antibodies of different isotypes or subtypes (e.g. IgG1, IgG2 etc.).^[2] Class switching will only occur to incorporate a heavy chain gene that resides downstream (in the immunoglobulin locus) from that of the original binding antibody.

The order (after the V, D, and J regions) is as follows:

• μ - IgM
• δ - IgD
• γ3 - IgG3
• γ1 - IgG1
• α1 - IgA1
• γ2 - IgG2
• γ4 - IgG4
• ε - IgE
• α2 - IgA2

Class switching occurs by a mechanism called class switch recombination (CSR). This process uses conserved nucleotide motifs, called switch (S) regions, found in DNA upstream from each of the antibody heavy chain constant region genes, except the δ-chain. DNA is nicked and broken at two selected S-regions by the activity of a series of enzymes, including Activation-Induced (Cytidine) Deaminase (AID), uracil DNA glycosylase and apyrimidic/apurinic (AP)-endonucleases.^[3][4] The intervening DNA between the S-regions is subsequently deleted from the chromosome, removing unwanted μ or δ heavy chain constant region genes and allowing substitution of the γ, α or ε constant region genes. The free ends of the DNA are rejoined by a process called non-homologous end joining (NHEJ) to link the variable domain exon to the desired downstream constant domain exon of the immunoglobulin heavy chain.^[5]

See also

• immunogenetics
• antibody

References

External links

• MeSH Immunoglobulin+class+switching
• Diagram and description at med.sc.edu (see Figure 10)
• Diagram at umassmed.edu
• Diagram and description at cam.ac.uk
• Diagram at utoronto.ca

•  • [ e] Immune system / Immunology
Systems	Adaptive immune system vs. Innate immune system • Humoral immune system vs. Cellular immune system • Complement system (Anaphylatoxins)
Antibodies and antigens	Antibody (Monoclonal antibodies, Polyclonal antibodies, Autoantibody) • Allotype • Isotype • Idiotype • Antigen (Superantigen)
Immune cells	White blood cells (T cell, B cell, NK cell, Mast cell, Basophil, Eosinophil) • Phagocyte (Neutrophil, Macrophage, Dendritic cell) • Antigen-presenting cell • Reticuloendothelial system
Immunity vs. tolerance	Immunity • Autoimmunity • Allergy • Tolerance (Central) • Immunodeficiency
Immunogenetics	Somatic hypermutation • V(D)J recombination • Immunoglobulin class switching • MHC / HLA
Other	Cytokines • Inflammation • Opsonin