SOMATIC DIVERSIFICATION OF IGH GENES IN RABBIT

Rabbits have helped elucidate one of the major immunologic puzzles, na mely the genetic control of antibody diversity The primary IgH antibod y repertoire in rabbits is dominated by B cells that use the same germ line V-H-gene segment in VDJ gene rearrangements. The VDJ genes of ess entially 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 hyp er-pointmutation. The diversification that occurs early in ontogeny ta kes place in gut-associated lymphoid tissues and potentially depends o n external factors such as microbial antigens. Few; if any, new B lymp hocytes develop in adult rabbits and we discuss how the antibody reper toire is maintained throughout life. Finally, we discuss the molecular mechanism of somatic gene conversion of Ig genes, including the possi bility that this involves the use of RAD51, an enzyme required for gen e conversion-mediated mating type switch in yeast.