Somatic diversification of IgH genes in rabbit.

Rabbits have helped elucidate one of the major immunologic puzzles, namely the genetic control of antibody diversity. The primary IgH antibody repertoire in rabbits is dominated by B cells that use the same germline VH-gene segment in VDJ gene rearrangements. The VDJ genes of essentially all B lymphocytes undergo somatic diversification within the first few weeks of the rabbit's life. Such diversification occurs both by a somatic gene conversion-like mechanism as well as by somatic hyperpointmutation. The diversification that occurs early in ontogeny takes place in gut-associated lymphoid tissues and potentially depends on external factors such as microbial antigens. Few, if any, new B lymphocytes develop in adult rabbits and we discuss how the antibody repertoire is maintained throughout life. Finally, we discuss the molecular mechanism of somatic gene conversion of Ig genes, including the possibility that this involves the use of RAD51, an enzyme required for gene conversion-mediated mating type switch in yeast.