COMPLEXITY OF THE IMMUNOGLOBULIN LIGHT CHAIN V-KAPPA-1 GENE FAMILY IN THE NEW-ZEALAND BLACK MOUSE

The immunoglobulin light chain V-kappa-1 gene family is polymorphic in murine inbred strains and this family has been subdivided into five sub-groups (V-kappa-1A-E). The V-kappa-1A sub-group contributes to approximately 2% of the total serum immunoglobulin light chains in several mouse strains. However, it has been reported that this sub-group is absent in New Zealand Black (NZB) mouse serum. Amino acid sequencing of myeloma proteins from this inbred mouse has shown that they belong to the V-kappa-1B sub-group. We report here the structure of nine functional germline genes from NZB mice that have high homologies to the V-kappa-1A, V-kappa-1B, V-kappa-1C, and V-kappa-1D sub-groups. In addition, a novel germline gene representing the prototype of a new sub-group (designated V-kappa-1F) has been identified. We have isolated different V-kappa-1 germline genes from a single restriction fragment length polymorphism (RFLP) fragment, as well as identical V genes from two different RFLP migrating bands. Therefore, the complexity of the genes encoding the immunoglobulin variable region cannot be determined solely by RFLP analysis. Nucleotide sequence analysis of 16 V-kappa-1 genes which code for NZB autoantibodies indicate that they belong to five different V-kappa-1 sub-groups with five hybridomas (31%) expressing the V-kappa-1A sub-group. Comparison of the sequences of V-kappa-1 genes expressed in hybridomas with corresponding germline genes shows no somatic mutations.