Contribution of human V kappa II germ-line genes to light-chain diversity.

The genetic basis of the antibody repertoire--estimated to exceed 10(6) different immunoglobulin molecules--is a major unanswered problem. The number of germ-line V kappa genes in the mouse genome is probably several hundred while the corresponding number for three out of four human V kappa subgroups (V kappa I, V kappa III and V kappa IV) is probably altogether only 15-20 (ref. 5). The kappa II proteins differ significantly in sequence from the other kappa-chain proteins. To determine the contribution of V kappa II genes to kappa-chain diversity, we searched for a human lymphoid cell line which produces a kappa II chain and report here for the first time the sequence of a V kappa II gene. According to blot hybridizations with this V kappa gene as a probe, subgroup II contributes about half as many genes to the V kappa gene repertoire as are detected by a V kappa I probe. Therefore the repertoire is rather small which implies that somatic mutations or other mechanisms must play an important role in the generation of light-chain diversity in humans.