A critical role for complement in maintenance of self-tolerance.
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
AP
The Center for Blood Research, Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Goerg
S
S
Shen
L M
LM
Pozdnyakova
O O
OO
Chu
L
L
Alicot
E M
EM
Goodnow
C C
CC
Carroll
M C
MC
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
D003176:Complement C3; D003181:Complement C4; D017463:Receptors, Complement 3b; D017464:Receptors, Complement 3d; D019014:fas Receptor; D003165:Complement System Proteins; D009113:Muramidase