title: A critical role for complement in maintenance of self-tolerance.
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.
authors.affiliation: The Center for Blood Research, Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: A P
authors.initials: AP
authors.lastname: Prodeus
authors.forename: S
authors.initials: S
authors.lastname: Goerg
authors.forename: L M
authors.initials: LM
authors.lastname: Shen
authors.forename: O O
authors.initials: OO
authors.lastname: Pozdnyakova
authors.forename: L
authors.initials: L
authors.lastname: Chu
authors.forename: E M
authors.initials: EM
authors.lastname: Alicot
authors.forename: C C
authors.initials: CC
authors.lastname: Goodnow
authors.forename: M C
authors.initials: MC
authors.lastname: Carroll
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology / Q000378:metabolism; D015551:Autoimmunity / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D017635:Clonal Anergy; D003176:Complement C3 / Q000172:deficiency; D003181:Complement C4 / Q000172:deficiency; D003165:Complement System Proteins / Q000276:immunology*; D005260:Female; D007108:Immune Tolerance / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009113:Muramidase / Q000378:metabolism; D017463:Receptors, Complement 3b / Q000172:deficiency; D017464:Receptors, Complement 3d / Q000172:deficiency; D019014:fas Receptor / Q000502:physiology
chemical_list: D003176:Complement C3; D003181:Complement C4; D017463:Receptors, Complement 3b; D017464:Receptors, Complement 3d; D019014:fas Receptor; D003165:Complement System Proteins; D009113:Muramidase