Figure 1.

Generation of antibody diversity. A number of different genes exist in three loci in the genome, for heavy chain [immunoglobulin (IG)H], kappa light chain (IGK) and for lambda light chain (IGL). Gene rearrangement occurs between the variable (IGHV), diversity (IGHD) and joining (IGHJ) regions of heavy chain, such that one of each type of gene is brought together with the help of recombination activating genes (RAG1 and RAG2). Similarly, the light chain genes are rearranged, either kappa or lambda, but without any diversity regions. Random recombination of heavy and light chain genes results in 9516 or 520 different combination possibilities, respectively. Random assortment of heavy and light chain gene rearrangements further increases the number of possibilities, in a multiplicative manner, to 4·9 × 10⁶. Inaccurate joining of the V(D)J regions further increases the possibility for diversity. Antibody CDR3 regions are at the junction of the different genes, and therefore the CDR3 regions have the highest diversity.