Antibodies somatic mutation

Bothwell, A.L.M., Paskind, M., Reth, M., Imanishi-Kari, T., Rajewsky, K., Baltimore, D. (1981). Heavy chain variable region contribution to the NPb family of antibodies somatic mutation evident in a y2a variable region. Cell 24,625-637. 

Lavoie, T. B., Drohan, W. N. and Smith-Gill, S. J. (1992), Experimental analysis by site-directed mutagenesis of somatic mutation effects on affinity and fine specificity in antibodies specific for lysozyme , f. Immunol., 148, 503-513. 

Chen, P.P, Liu M.F., Sinha S., et al. (1988). A 16/6 idiotype-positive anti-DNA antibody is encoded by a conserved VH gene with no somatic mutation. Arthritis Rheum., 31, 1429-1431. 

Seal, S.N., Hoet, R.M.A., Raats, J.M.H., Radic, M.Z. (2000). Analysis of autoimmune bone marrow by antibody phage display, Somatic mutations and CDR3 Arginines in anti-DNA and V genes. Arthritis. Rheum., 43, 2132-2138. 

Antibodies have been studied most extensively in the mouse, an ideal vertebrate for both genetic and biochemical manipulations. It is believed that mice can synthesize more than a million antibodies with different antigenic specificities. This enormous diversity of proteins is generated from a limited amount of genetic information with the help of two mechanisms Somatic recombination and somatic mutation. 

Somatic Mutation Contributes to Antibody Diversity. Various estimates, some exceeding a million, have been put... 

The first persuasive, albeit indirect, evidence that antibodies are diversified by somatic mutation came from the analysis of mouse X light chains by Weigert et al. (1970). In the initial experiments, V regions of ten X chains, obtained from mouse plasmacytomas, were examined by peptide mapping and partial sequence analysis. 

Crews, S., Griffin, J., Huang, H., Calame, K., Hood, L. (1981). A single VH gene segment encodes the immune response to phosphorylcholine somatic mutation is correlated with the class of the antibody. Cell 25, 59-66. 

Diamond, B., Scharff, M.D. (1984). Somatic mutation of the T15 heavy chain gives rise to an antibody with autoantibody specificity. Proc. Natl. Acad. Sci. USA 81, 5841-5844. 

Manser, T., Parhami-Seren, B., Margolies, M.N., Gefter, M.L. (1987). Somatically mutated forms of a major anti-p-azophenylarsonate antibody variable region with drastically reduced affinity for p-azophenylarsonate. By-products of an antigen-driven immune response J. Exp. Med. 166, 1456-1463. 

Anti-dsDNA Antibodies Are Antigen-Driven. There is evidence that variable regions of both heavy and light chains of both murine and human monoclonal anti-dsDNA antibodies are produced after an affinity maturation process via isotype switching, clonal selection, and somatic mutation (D5, D9, Wll, C16, V3). These findings suggest that anti-dsDNA antibodies are produced by an... 

G7. Gilkeson, G. S., Bernstein, K. A., Pippin, A. M. M., Clark, S. H., Marion, T., etal., The influence of variable region somatic mutations on the specificity and pathogenicity of murine monoclonal anti-DNA antibodies. Clin. Immunol. Immunopathol. 68, 283-292 (1993). 

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