Question

Outline the mechanism for antibody class switching. Include typical class switching in mucosa and blood, and which parts of the antibody are affected and which are unaffected.

Answer 1

Antibody Class Switch Recombination (CSR) is a biological mechanism by which B cells production of antibody is changed from one class to another; for example from an isotype IgM to isotype IgG. The antibody isotype of a B cell changes during cell development and activation. When the immature B cells known as naive B cells exposed to an antigen for the first time then they express only IgM isotype on B cell surface receptor. On reaching maturity, B cells express both IgM and IgD isotypes and renders the B cell mature to respond to antigen. B cell activation causing the cells to divide and differentiate into antibody producing cells called plasma cells. Now this activated B cells when encounter specific signaling molecules via their CD40 and cytokine receptors (both modulated by helper T cells), they undergo antibody class switching to produce IgG, IgA and IgE antibodies.

Class switching by a mechanism called class switch recombination (CSR) binding. During CSR, the constant region of the heavy chain is changed without altering the variable region, thus class switching does not affect antigen specificity. A portion of the antibody heavy chain locus are removed from the chromosome and the genes around the deleted portion are rejoined to retain a functional antibody gene that produces different antibody isotypes. Double strand breaks (DSBs) are generated in DNA at conserved nucleotide sequence, known as Switch (S) region which are located upstream from the gene segments that encode constant regions of the antibody heavy chain. This event takes place in all the genes adjacent to heavy chain constant region except the -chain. DNA is cut and broken at two selected S regions mediated by a series of enzymes which includes Activation-induced (cytidine) deaminase (AID), uracil DNA glycosylase and apyrimidic/apurinic (AP) endonucleases. The intervening region between the S regions is deleted from the chromosome removing unwanted   or heavy chain constant region exons and permiting substitution of , or constant region gene segment exons. The free ends of the DNA are rejoined by a process called non homologous end joining.

The immunoglobulins abundant in mucosa and bllod are IgA and IgG respectively. Typical class switching in mucosa and blood includes the switching of IgM and IgD antibody isotype to IgA and IgG respectively. The heavy chain exons are as follows: (IgM), (IgD), (IgG), (IgA) and (IgE). For the class switchng to IgA and IgG, the unwanted    or heavy chain constant region exons are removed along with the removal of exons that encode for IgE. So the unaffected parts of antibody heavy chain constant region includes and .