SOMATIC HYPERMUTATION - MUTATIONS-3' OF RABBIT VDJ H-CHAIN GENES

VDJ genes of rabbit B cells are diversified by a somatic gene conversi on-like mechanism in which V-H gene segments 5' of the VDJ gene serve as donors. To assess whether somatic mutation also contributes to Ab d iversification in the rabbit, we searched for mutations 3' of VDJ gene s because mutations in this region presumably result from somatic muta tion rather than gene conversion. We PCR-amplified and cloned the regi on extending 534 bp 3' of VDJ genes from splenic DNA of young and adul t rabbits, Results of nucleotide sequence analysis of the clones revea led a high mutation frequency (2.4%) within the first 120 bp downstrea m of VDJ genes. This frequency decreased rapidly with increasing dista nce 3' of the VDJ genes. The mutations demonstrated both strand bias a nd dinucleotide preferences characteristic of somatic hypermutation. W e conclude that Ab diversity in rabbit is generated not only by somati c gene conversion but also by somatic hypermutation.