Contribution of human VκII germ-line genes to light-chain diversity

Abstract

The genetic basis of the antibody repertoire—estimated to exceed 106 different immunoglobulin molecules—is a major unanswered problem1,2. The number of germ-line Vκ genes in the mouse genome is probably several hundred3,4 while the corresponding number for three out of four human Vκ subgroups ( VκI, VκIII and VκIV) is probably altogether only 15–20 (ref. 5). The κII proteins differ significantly in sequence from the other κ-chain proteins6. To determine the contribution of VκII genes to κ-chain diversity, we searched for a human lymphoid cell line which produces a κ II chain and report here for the first time the sequence of a VκII gene. According to blot hybridizations with this Vκ gene as a probe, subgroup II contributes about half as many genes to the Vκ gene repertoire as are detected by a VκI probe. Therefore the repertoire is rather small which implies that somatic mutations7–9 or other mechanisms must play an important role in the generation of light-chain diversity in humans.