Immunoglobulin structure and function: genetic control of antibody diversity.

Recent studies of the molecular biological characteristics of lymphoid cells have markedly increased our understanding of how millions of different antibodies can be synthesized by an individual mammal. In particular, studies have shown how antibody genes are arranged and rearranged within B-lymphocyte clones to provide each cell clone with antibody of defined specificity for antigen. The process involves the assembly, from disparate genetic elements, of a complete antibody gene that will code for an antibody protein. The assembly process, in itself, also provides mechanisms for generating the diversity of antibody variable region structure (that part of an antibody molecule that actually binds antigen) that is essential to a full role for humoral immunity in host defense mechanisms. Specifically, the diversity of structure characteristic of mature antibodies derives from 3 distinct mechanisms: innate variability of germ-line genes; mismatching of individual gene segments during their somatic rearrangement leading to junctional diversity; and somatic mutation in variable region genetic material during or after the rearrangement. Thus, it is now clearly understood that several processes are involved in explaining the origin of the antigen-combining diversity of antibody proteins. Certain "lottery-like" aspects of these genetic processes add to the combinatorial possibilities that are characteristic of the humoral immune system.