A critical role for complement in maintenance of self-tolerance

Immunity. 1998 Nov;9(5):721-31. doi: 10.1016/s1074-7613(00)80669-x.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / metabolism
  • Autoimmunity / immunology
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • Clonal Anergy
  • Complement C3 / deficiency
  • Complement C4 / deficiency
  • Complement System Proteins / immunology*
  • Female
  • Immune Tolerance / immunology*
  • Lymphocyte Activation / immunology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Muramidase / metabolism
  • Receptors, Complement 3b / deficiency
  • Receptors, Complement 3d / deficiency
  • fas Receptor / physiology


  • Complement C3
  • Complement C4
  • Receptors, Complement 3b
  • Receptors, Complement 3d
  • fas Receptor
  • Complement System Proteins
  • Muramidase