16.1 Rearrangement of gene in B and T lymphocytes

The genes responsible for the diverse antigen receptors on B and T cells are generated by the arrangement of variable (V), diversity (D), and joining (J) regions in the gene segment. This phenomenon of rearrangement of chromosomal segment is called V (D) J recombination . The V(D)J recombination is the reason for the diversity of the immune cells in the body. This was proved by Susumu Tonegawa who demonstrated that DNA segments in the loci responsible for light and heavy chain of an immunoglobulin molecule is different in developing B cells than in any other cell types.

16.1.1 Organization of immunoglobulin and T cell receptor gene

The organization of the germline genetic loci of immunoglobulin and T cell receptor gene are similar in terms of their organization.

The immunoglobulin heavy chain is encoded by chromosome 14, κ light chain by chromosome 2, and λ light chain by chromosome 22. The 5' end of the gene contains clusters for the variable region of around 300bp. The joining segments start after the variable region, which is around 30-50 bp long. The diversity region occupies the space between the variable and joining region. The length and size of these three V, D and J regions varies among different species of animals. The immunoglobulin locus also contains different constant region that encodes the C chain of the Ig molecule.

The T cell receptor α and δ chains are encoded by chromosome 14 while β and γ chains by chromosome 7. The loci on the T cells are similar to that of the immunoglobulin. The detailed structure of the genome orientation for both B and T cells are beyond the scope of this course.

16.1.2 V(D)J recombination

The germline genes cannot be transcribed into mRNAs that encode the functional receptor proteins. The functional genes are only generated in developing B and T lymphocytes after rearrangement of V, (D), and J chains. The process involves the selection of one segment of each V, (D), and J chains in any lymphocyte and arrange it into a single exon that encodes the variable region of an antigen receptor. Conserved heptamer (7 bp) and nonamer (9 bp) are located adjacent to the V and J exons. The V (D) J recombinase recognizes these signals and brings the segments together. The specific factors that mediate the V, (D), and J chain recombination recognizes the recombination signal sequences (RSS) that are located at 3' end of V and 5' end of J segment. The V and J chain combine together after deletion of the intervening sequence or inversion of the sequence if they are oriented in the opposite direction.