Abstract
THE mechanism by which the immune system produces an apparently limitless array of antibodies in response to a variety of antigenic stimuli remains an unresolved biological question. Primary structural analysis has shown that immunoglobulin heavy (H) and light (L) chains have both variable (V) and constant (C) regions of amino acid sequence. Within the VH and VL region sequences there are areas of hypervariability which are thought to be associated with the antibody combining site. It is the amino acid substitutions within certain of these hypervariable areas that result in the multiplicity of antibody specificities (sites) expressed in nature. It seems clear that separate genes code for the V and C regions of H and L chains and that integration of V- and C-region genes occurs at the DNA level1. One can account for antibody isotypic diversity by postulating a limited number of C-region genes which are transmitted from generation to generation in the germ line. The difficulty arises in the attempt to account for the apparent large numbers of V-region genes required to explain antibody combining site diversity. V-gene counting has been accomplished by RNA–DNA hybridisation2–4. Evidence from these studies has not definitely demonstrated whether the capacity to generate large numbers of combining sites exclusively arises by either the inheritance of a complete set of VH and VL genes in the germ line or by somatic mutation. The repeated occurrence of V-gene products has, however, been indicated by sequence analysis of myeloma proteins5–7, isoelectric focusing8–10, and idiotypic analysis11–13.
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MONTGOMERY, P., SKANDERA, C. & KAHN, R. Evidence for the induction of two antibodies with identical combining sites in outbred animals. Nature 256, 138–140 (1975). https://doi.org/10.1038/256138a0
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DOI: https://doi.org/10.1038/256138a0
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