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 VH genes. This preferential usage of one gene, VH1, raises the question of how rabbits generate antibody diversity. VDJ diversification was analyzed by cloning and sequencing VH1 gene rearrangements. Comparison of these sequences with that of germline VH1 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 VH gene sequences for donor VH 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.