Most kappa immunoglobulin mRNA in human lymphocytes is homologous to a small family of germ-line V genes.

The mammalian immune system produces 10(6)-10(8) different antibody-combining sites. It has been established that three factors contribute to the diversity of immunoglobulin variable regions: multiple gene segments in the germ line, somatic recombination of these segments and somatic mutation. However, the relative importance of these components in generating the antibody repertoire is unknown. One way to assess the importance of the germ-line component relative to the somatic components would be to determine the number of germ-line V genes expressed. Here, I report that a family of about 25 human germ-line V genes encodes over 50% of kappa mRNA in spleen or peripheral blood lymphocytes. This observation agrees with gene-counting experiments which indicated that the total number of V kappa genes in the human genome is quite small, about 50 or less. Such a small number of germ-line V kappa sequences implies that somatic mutation is the major source of human kappa-chain diversity.