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

• Published in: Nature (London) 1981-06, Vol.291 (5817), p.668-670
• Main Authors: Pech, Michael, Höchtl, Josef, Schnell, Hannelore, Zachau, Hans G
• Format: Article
• Language: English
• Subjects: Animals; Base Sequence; Binding Sites, Antibody - genetics; Cell Line; Cloning, Molecular; DNA Restriction Enzymes; DNA, Recombinant; Genes; Humanities and Social Sciences; Immunoglobulin J-Chains - genetics; Immunoglobulin kappa-Chains - genetics; Immunoglobulin Light Chains - genetics; Immunoglobulin Variable Region - genetics; letter; Mice; multidisciplinary; Mutation; Plasmacytoma; Science; Science (multidisciplinary)
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/291668a0

Several mechanisms contribute to the generation of an antibody repertoire (for reviews see refs 1–3) which has been estimated to exceed 10 6 different types of immunoglobulin molecules 4 . 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 diversity 12 . 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 chain 14 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.