A critical role for complement in maintenance of self-tolerance

The role of complement in the maintenance of self-tolerance has been examin ed in two models: an immunoglobulin transgenic model of peripheral toleranc e and a lupus-like murine model of CD95 (Fas) deficiency. We find that self -reactive B lymphocytes deficient in complement receptors CD21/CD35 or tran sferred 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 antib odies 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 sy stemic lupus erythematosus.