IGM is required for efficient complement mediated phagocytosis of apoptotic cells in vivo.
A variety of complement components have been detected on apoptotic cells and proposed to facilitate recognition and/or ingestion by phagocytes. The triggers for complement activation remain uncertain. To determine the role of IgM in classical pathway activation and clearance of apoptotic cells in vitro and in vivo, we quantified these parameters in mice deficient in serum IgM (sIgM). Phagocytosis by bone marrow-derived macrophages of apoptotic cells incubated with serum deficient in sIgM was markedly reduced, similar to apoptotic cells incubated with C1q deficient serum in vitro. Similarly, intraperitoneal clearance of apoptotic cells and cellular C3 deposition were significantly reduced in mice deficient in sIgM compared to wild-type mice. Clearance and C3 deposition were reconstituted by addback of IgM. In mice deficient in both sIgM and Clq, addback of both serum factors was required for restoration of clearance. These findings indicate that, on a quantitative basis, sIgM is a potent factor required for intraperitoneal phagocytosis of apoptotic cells, and further demonstrate that IgM and C1q work in concert to activate complement, resulting in C3 deposition on the apoptotic cell surface and ultimately, efficient clearance of the apoptotic cell by macrophages.
Ogden
Carol Anne
CA
Division of Rheumatology and Immunology, University of Washington, Seattle, WA 98195, USA.
Kowalewski
Robert
R
Peng
Yufeng
Y
Montenegro
Vivianne
V
Elkon
Keith B
KB
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D015922:Complement C1q / Q000276:immunology*; D003176:Complement C3 / Q000276:immunology*; D003171:Complement Pathway, Classical / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology*; D019169:Jurkat Cells; D017737:Macrophages, Peritoneal / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010587:Phagocytosis / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D003176:Complement C3; D007075:Immunoglobulin M; D015922:Complement C1q