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Role of Complement C4 in the Regulation of Self‐Reactive B Cells
Author(s) -
AGYEMANG AMMA,
ALIMZHANOV MARAT B,
IMANISHIKARI THEREZA,
CARROLL MICHAEL C
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.2_supplement.478
Subject(s) - antibody , immunology , complement system , complement receptor , immune system , biology , b cell , antigen , alternative complement pathway
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by nephritis, arthritis, dermatitis and antibody production against nuclear antigens. In humans and mice, deficiency in the classical complement components C1, C2 and C4 is strongly associated with SLE. Studies suggest that complement proteins ameliorate SLE by enhancing the 1) efficient removal of immune complexes and apoptotic debris and/or 2) negative selection of developing B cells. In this study, we used the 564 immunoglobulin (Ig) heavy and light chain knock‐in mouse model on a C4‐deficient or complement receptor 1/2 (CR1/2) deficient background to examine the effects of complement C4 on the regulation of nuclear antigen specific (NAS) B cells. In control mice, NAS B cells were negatively selected. Those that escaped had an immature, anergic phenotype and were excluded from B cell follicles. C4 −/− 564Ig and CR1/2 −/− 564Ig NAS B cells differentiated into non‐anergic, mature B cells without follicular exclusion. Production of anti‐nuclear antibodies was detected in both C4 −/− 564Ig mice and controls. However, specific antibody deposition in kidneys was only observed in C4 −/− 564Ig mice. These data suggest that complement C4 is involved in negative selection of NAS B cells and clearance of potentially pathogenic antibodies. This role of complement C4 may be partially dependent on complement receptors CR1 and CR2.