A critical role for complement in maintenance of self-tolerance

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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.




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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