title: Antigen-induced B cell apoptosis is independent of complement C4.
abstract: 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.
authors.affiliation: Institute of Immunology and Transfusion Medicine, University of Luebeck, Luebeck, Germany.
authors.forename: K B
authors.initials: KB
authors.lastname: Faust
authors.forename: D
authors.initials: D
authors.lastname: Finke
authors.forename: K
authors.initials: K
authors.lastname: Klempt-Giessing
authors.forename: K
authors.initials: K
authors.lastname: Randers
authors.forename: B
authors.initials: B
authors.lastname: Zachrau
authors.forename: P
authors.initials: P
authors.lastname: Schlenke
authors.forename: H
authors.initials: H
authors.lastname: Kirchner
authors.forename: S
authors.initials: S
authors.lastname: Goerg
mesh_terms: 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
chemical_list: D000941:Antigens; D003181:Complement C4; D009596:Nitrophenols; D010648:Phenylacetates; C026242:4-hydroxy-5-nitrophenyl acetic acid