A critical role for complement in maintenance of self-tolerance |
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Authors: | AP Prodeus S Goerg LM Shen OO Pozdnyakova L Chu EM Alicot CC Goodnow MC Carroll |
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Affiliation: | The Center for Blood Research, Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA. |
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Abstract: | The role of complement in the maintenance of self-tolerance has been examined in two models: an immunoglobulin transgenic model of peripheral tolerance and a lupus-like murine model of CD95 (Fas) deficiency. We find that self-reactive B lymphocytes deficient in complement receptors CD21/CD35 or transferred into mice deficient in the complement protein C4 are not anergized by soluble self-antigen. In the second model, deficiency in CD21/CD35 or C4 combined with CD95 deficiency results in high titers of anti-nuclear antibodies leading to severe lupus-like disease. These findings suggest a novel role for the complement system in B cell tolerance and provide insight into the genetic association of complement deficiency with susceptibility to systemic lupus erythematosus. |
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