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Anti-DNA antibodies from autoimmune mice arise by clonal expansion and somatic mutation.

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  • 1. Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111.
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    • Shlomchik M 1
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The Journal of Experimental Medicine, 01 Jan 1990, 171(1):265-292
https://doi.org/10.1084/jem.171.1.265 PMID: 2104919 PMCID: PMC2187662

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Abstract 

The proximate cause of autoantibodies characteristic of systemic autoimmune diseases has been controversial. One hypothesis is that autoantibodies are the result of polyclonal nonspecific B cell activation. Alternatively, autoantibodies could be the result of antigen-driven B cell activation, as observed in secondary immune responses. We have approached this question by studying monoclonal anti-DNA autoantibodies derived from unmanipulated spleen cells of the autoimmune MRL/lpr mouse strain. This analysis shows that anti-DNAs, like rheumatoid factors (19), are the result of specific antigen-driven stimulation. In addition, correlation of sequences with fine specificity shows that: (a) somatic mutations can cause specificity for dsDNA and that such mutations are selected for; (b) arginine residues play an important role in determining specificity; and (c) anti-idiotypes that recognize the majority of anti-DNA are probably not specific for any one family of V regions.

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J Exp Med. 1990 Jan 1; 171(1): 265–292.
PMCID: PMC2187662
PMID: 2104919

Anti-DNA antibodies from autoimmune mice arise by clonal expansion and somatic mutation

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Abstract

The proximate cause of autoantibodies characteristic of systemic autoimmune diseases has been controversial. One hypothesis is that autoantibodies are the result of polyclonal nonspecific B cell activation. Alternatively, autoantibodies could be the result of antigen-driven B cell activation, as observed in secondary immune responses. We have approached this question by studying monoclonal anti- DNA autoantibodies derived from unmanipulated spleen cells of the autoimmune MRL/lpr mouse strain. This analysis shows that anti-DNAs, like rheumatoid factors (19), are the result of specific antigen-driven stimulation. In addition, correlation of sequences with fine specificity shows that: (a) somatic mutations can cause specificity for dsDNA and that such mutations are selected for; (b) arginine residues play an important role in determining specificity; and (c) anti- idiotypes that recognize the majority of anti-DNA are probably not specific for any one family of V regions.

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