The molecular origin of anti-DNA antibodies

International Reviews of Immunology
S M BeharM Scharff

Abstract

The in vitro observation that a single point mutation in the protective anti-phosphorylcholine anti-bacterial antibody, S107, converts it into an autoantibody that reacts with dsDNA has focused our attention on the role of somatic mutation in generating autoantibodies. It has also led us to examine the significance of an individual's prior response to environmental antigens on the subsequent production of autoantibodies. The fact that genes of the S107 heavy chain variable region family could encode autoantibodies made it possible to clone and sequence the relevant germline genes of this small family from autoimmune (NZB x NZW)F1 mice and to compare these to the comparable genes in non-autoimmune mice. The germline genes from the normal and autoimmune mice are quite homologous and the small number of polymorphisms are not likely to predispose the autoimmune mice to the production of autoantibodies. (NZB x NZW)F1 mice respond to immunization with phosphorylcholine with a response that is largely encoded by the VH1 gene of the S107 family. However, when these same mice begin to make autoantibodies, their anti-DNA antibodies which are encoded by this family are in fact derived from the VH11 gene. The VH11 encoded anti-DNA antibodi...Continue Reading

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Citations

Mar 11, 1992·Molecular Immunology·M Chao, E W Voss
Aug 6, 1996·Proceedings of the National Academy of Sciences of the United States of America·Y WangL A Matis
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Oct 11, 2007·The Journal of Biological Chemistry·Gagik OganesyanGenhong Cheng
Jan 1, 1994·International Reviews of Immunology·A Shirai, D M Klinman

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