Antigen-induced B cell apoptosis is independent of complement C4.
Deficiencies in early complement components are associated with the development of systemic lupus erythematosus (SLE) and therefore early complement components have been proposed to influence B lymphocyte activation and tolerance induction. A defect in apoptosis is a potential mechanism for breaking of peripheral B cell tolerance, and we hypothesized that the lack of the early complement component C4 could initiate autoimmunity through a defect in peripheral B lymphocyte apoptosis. Previous studies have shown that injection of a high dose of soluble antigen, during an established primary immune response, induces massive apoptotic death in germinal centre B cells. Here, we tested if the antigen-induced apoptosis within germinal centres is influenced by early complement components by comparing complement C4-deficient mice with C57BL/6 wild-type mice. We demonstrate that after the application of a high dose of soluble antigen in wild-type mice, antibody levels declined temporarily but were restored almost completely after a week. However, after antigen-induced apoptosis, B cell memory was severely limited. Interestingly, no difference was observed between wild-type and complement C4-deficient animals in the number of apoptotic cells, restoration of antibody levels and memory response.
Faust
K B
KB
Institute of Immunology and Transfusion Medicine, University of Luebeck, Luebeck, Germany.
Finke
D
D
Klempt-Giessing
K
K
Randers
K
K
Zachrau
B
B
Schlenke
P
P
Kirchner
H
H
Goerg
S
S
D000818:Animals; D000941:Antigens / Q000276:immunology; D017209:Apoptosis / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D003181:Complement C4 / Q000172:deficiency* / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D018858:Germinal Center / Q000276:immunology; D007108:Immune Tolerance; D007156:Immunologic Memory; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009596:Nitrophenols / Q000276:immunology; D010648:Phenylacetates
D000941:Antigens; D003181:Complement C4; D009596:Nitrophenols; D010648:Phenylacetates; C026242:4-hydroxy-5-nitrophenyl acetic acid