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