Somatic diversification of immunoglobulin heavy chain VDJ genes: Evidence for somatic gene conversion in rabbits

Rabbits preferentially utilize only one of their multiple functional germline Immunoglobulin V H genes. This preferential usage of one gene, V H1 , raises the question of how rabbits generate antibody diversity. VDJ dlversification was analyzed by cloning and sequencing V H1 gene rearrangements. Comparison of these sequences with that of germline V H1 identified clusters of nucleotide changes, including codon insertions and deletions. To investigate whether gene conversion was involved in this somatic diversification, we searched a data base of rabbit germline V H gene sequences for donor V H genes; potential donors were identified for five diversified regions. We conclude that somatic gene conversion has a major role in generating antibody diversity in rabbits. These studies provide clear evidence for somatic gene conversion of mammalian VDJ genes.