The role of clonal selection and somatic mutation in autoimmunity

来自 EBSCO

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作者：

MJ Shlomchik，A Marshak-Rothstein，CB Wolfowicz，TL Rothstein，MG Weigert

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摘要：

Polyclonal activation has been proposed as the reason that auto-antibodies are produced during autoimmune disease 1–3 . This model denies a role for specific antigen selection of B cells and predicts instead a multiclonal population of unmutated or randomly mutated autoantibodies. We have found that the genetic features and clonal composition of spontaneously derived immunoglobulin G (IgG) antiself-IgG (rheumatoid factor (RF)) autoantibodies derived from the autoimmune MRL/ lpr mouse strain are inconsistent with both the predictions of this model and the actual outcome of experimental polyclonal activation 4,5 . Instead we have found that MRL/ lpr RFs are oligoclonal or even monoclonal in origin. They harbour numerous somatic mutations which are distributed in a way that suggests immunoglobulin-receptor-depen-dent selection of these mutations. In this sense, the MRL/ lpr RFs resemble antibodies elicited by exogenous antigens after secondary immunization 6–8 . The parallels suggest that, like secondary immune responses, antigen stimulation is important in the generation of MRL/ lpr RFs.

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关键词：

IMMUNODETECTION TECHNIQUES MONOCLONAL ANTIBODIES WATER MICROORGANISMS TOXINS

DOI：

10.1038/328805a0

被引量：

1581

年份：

1987