Diversity in the rabbit immunoglobulin kappa chain variable regions is amplified by nucleotide deletions and insertions at the V-J junction.

To analyze the rabbit immunoglobulin kappa locus, we isolated, from a phenotypically homozygous b4/b4 rabbit genomic library, a C kappa gene corresponding to the b4 var allelic form of the b4 C kappa gene. We also determined the nucleotide sequence of the J kappa cluster 3 kb upstream of the b4 var C kappa gene. Southern blot experiments with rabbit J kappa probes indicate that the bas C kappa gene is an isotype probably associated with its own J kappa segment(s). The rabbit b4 J kappa gene region contains a cluster of five J kappa segments, homologous to the human J kappa cluster, and two remnant J kappa segments approximately 5 kb upstream of the b4 C kappa gene. Nucleotide sequence analyses of the coding J kappa segments and their recombination signal sequences show only one functional J kappa segment. Comparisons with the protein data indicate that the rabbit kappa gene family, unlike its human and mouse homologs, increases kappa light chain variability by deletions and insertions at the V-J junction.