Antigen-induced B cell apoptosis is independent of complement C4

Abstract

SummaryDeficiencies 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.

Gene Expression Profiling Distinguishes Radiation-Induced Fibrosing Alveolitis from Alveolitis in Mice

“…Created by gene targeting and shown to lack C4 in the serum (11), this model of C4b deficiency has been studied for complement involvement in collagen-induced arthritis (20), B cell function (21) and the development of glomerulonephritis (22) among other traits. The response of these mice to thoracic irradiation had not been documented, but, as evaluated here using standard markers of radiation-induced lung disease (5,23,24), no differences in response from wild-type littermates were evident.…”