A mechanism for generating diversity of antibodies in B cells and of receptors in T cells (see T-cell receptor). The variable regions of an antibody's light (VL) and heavy (VH) chains, which determine the molecule's binding properties for antigen, are encoded by genes that are assembled from either two (in the case of VL) or three (for VH) gene segments. The two segments of a VL gene are a V gene segment and a J(or joining) gene segment. The human λ light chain genetic locus on chromosome 22 has a cluster of roughly 30 V gene segments and four pairs of J gene segments. So there are potentially 4 × 30 = 120 different combinations, meaning that 120 different VH regions can be made. Adding to this the 200 possible combinations for the second type of light chain (κ light chains, encoded by a gene cluster on chromosome 2) makes 320 different light chains. Heavy chain genes contain a third gene segment, called a diversity (or DH) gene segment, and possible combinations of the V, DH, and J segments found at the heavy chain locus on chromosome 14 total roughly 6000. Therefore, altogether there are theoretically 1.9 × 106 (i.e. 320 × 6000) different antibodies possible. This enables B cells to generate their vast repertoire of antibodies to match the great diversity of possible antigens. The recombination mechanism, called V(D)J recombination, is a multistep enzymatic process requiring the products of two genes that are expressed only in developing lymphocytes, namely the recombination-activating genes RAG1 and RAG2. Diversity of T-cell receptors is generated by a similar mechanism involving the rearrangement of gene segments encoding variable regions of the α and β chains. See also somatic hypermutation.
Subjects: Biological Sciences.