Differences between germ-line and rearranged immunoglobulin V_κ coding sequences suggest a localized mutation mechanism

Abstract

Several mechanisms contribute to the generation of an antibody repertoire (for reviews see refs 1–3) which has been estimated to exceed 10⁶ different types of immunoglobulin molecules⁴. It is clear that the germ line contains a fair number of V-gene segments^2,5–7. The V-gene segments are joined by somatic recombination to J- and D-gene segments^8–11 and there is, of course, combinatorial association of heavy and light chains. It has been suggested that the germ-line repertoire of gene segments and their combinatorial joining are the principal sources of antibody diversity¹². In fact, two rearranged V_κ-gene segments have been found to be identical in sequence to their germ-line counterparts^12,13, showing that no somatic point mutations had occurred. In the genes for a λ_I light chain¹⁴ and for two heavy chains^10,15, on the other hand, the rearranged V-gene segments differed in several positions from their germ-line equivalents; this is explained by somatic point mutations. We now report the finding of six single-base pair differences each between two rearranged V_κ-gene segments and their presumptive germ-line equivalents and the absence of any such differences in the adjacent non-coding regions; this suggests the existence of localized mutation mechanism(s) in this V_κ gene system.