Question

Can someone summarize the V(D)J recombination, class switch recombination (CSR) and somatic hypermutation (SHM) with the mechanism in relationship to antigen and antibody.

Answer 1

V(D)J recombination:

*it is also known as somatic recombination.

* in this process,gene segments combine randomly during the development of B- cells.

*firstly, one random D and one J gene segment of the heavy chain locus undergoes recombination.

*DNA between theses 2 gene segments are deleted and hence D and J gene segments come close to each other.

*this D -J recombination is then followed by combination of one random V gene segment ,forming a rearranged V(D)J gene segment.

*This process occurs in bone marrow and the light chain locus is arranged in a very similar way except that it lacks the D segment,so only VJ recombination takes place.

*following successful  recombination of light and heavy chain ,mature B lymphocytes   express IgM and IgD on the  surface and migrate to secondary lymphoid organs like lymph nodes and spleen where they interact with antigens.

Somatic hypermutation(SHM):

*occurs in the V region of of both H and L chain genes.

*it helps to create diversity and is displayed by adaptive immune response.

*here, the B cells are allowed to mutate genes which are used to produce antibodies.

*mutation occurs due to nucleotide substitution rather than addition or deletion.

*main site of mutations are the hypervariable regions( sites involved in antigen recognition on the antibody)

*SHM followed by selection leads to formation of high affinity antibodies.

Class switch recombination(CSR):

*It is another biological mechanism which changes the expression og the immunoglobulin from IgM to another isotype (ie. IgG , IgA or IgE).

*This process changes the functional properties and antibody structure.

*Since CSR is limited to constant region of heavy chain , it doesnot affect antigen specificity.(it is the variable regions of light and heavy chains that encode the antigen specificity).

*Here, the antibody retains affinity for same antigen ,but can interact with different effector molecules.

*In isotype switching,   and H chain C (C_H) regions of the expressed immunoglobulin are replaced with , or C_H  regions .

*CSR is a deletional DNA recombination occuring between switch regions.

*Here, recombination occurs between dsDNA breaks(DSBs) introduced into donor S region and an acceptor S region located downstream.