A critical role for complement in maintenance of self-tolerance

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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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Prodeus, A. P., Goerg, S., Shen, L. M., Pozdnyakova, O. O., Chu, L., Alicot, E. M., … Carroll, M. C. (1998). A critical role for complement in maintenance of self-tolerance. Immunity, 9(5), 721–731. https://doi.org/10.1016/S1074-7613(00)80669-X

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