[Molecular mechanisms of antibody synthesis]

Antibodies or immunoglobulins play a central part in the immune system. The basic unit of an antibody is composed of two identical light and two identical heavy chains; each chain contains two functionally and structurally distinct regions: an amino-terminal variable or antigen-binding site, and a carboxy-terminal constant region responsible for immunological effector functions. Thanks to recombinant DNA technology the paradox of a limited number of genes and a virtually unlimited capacity to generate specific antibodies has now been resolved at least in outline. Immunoglobulin chains are encoded in multiple gene segments of three unlinked gene families scattered along chromosomes 2 (kappa light chain), 14 (heavy chain) and 22 (lambda light chain). During B-cell differentiation these genes are assembled by somatic recombination mechanisms to form active genes. The enormous diversity generated by means of DNA rearrangements is supplemented by mutations somatically introduced into variable region sequences. The medical impact of these discoveries will be substantial. Possible applications include identification of B-cell precursors lacking conventional markes, a molecular classification of lymphomas and a precise distinction between monoclonal and polyclonal lymphoproliferative disorders.