[Immunoglobulin genes and the origin of antibody diversity]

The genes encoding for the heavy, Kappa and Lambda chains of immunoglobulins are located on separate chromosomes. Each gene consists of many segments encoding for variable (V) and constant (C) domains of immunoglobulins. Each V gene is assembled from individual segments of germline, VL and JL for the light chains, VH, D and JH for the heavy chains. There are several hundreds VH and VL segments and a small number of D and JH segments. A complete VH gene (VH-D-JH combination) is first expressed in association with the nearest C region gene (C mu) but a class switch recombination may occur, enabling the same VH to associate with C regions of gamma, alpha or epsilon type. The generation of the antibody diversity is explained by several mechanisms: a) the rearrangements of the segments encoding for the variable domains (related to the presence of many segments and the joining variability between these segments); b) the combinations between heavy and light chains; c) the occurrence of somatic mutations in the DNA encoding for VH and VL gene segments.