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IgM Antibodies to Apoptosis-Associated Determinants Recruit C1q and Enhance Dendritic Cell Phagocytosis of Apoptotic Cells¹

Laboratory of B-cell Immunobiology, Department of Medicine, University of California at San Diego, La Jolla, CA 92093

Natural Abs, which arise without known immune exposure, have been described that specifically recognize cells dying from apoptosis, but their role in innate immunity remains poorly understood. Herein, we show that the immune response to neoantigenic determinants on apoptotic thymocytes is dominated by Abs to oxidation-associated Ags, phosphorylcholine (PC), a head group that becomes exposed during programmed cell death, and malondialdehyde (MDA), a reactive aldehyde degradation product of polyunsaturated lipids produced following exposure to reactive oxidation species. While natural Abs to apoptotic cells in naive adult mice were dominated by PC and MDA specificities, the amounts of these Abs were substantially boosted by treatment of mice with apoptotic cells. Moreover, the relative amounts of PC and MDA Abs was affected by V_H gene inheritance. Ab interactions with apoptotic cells also mediated the recruitment of C1q, which enhanced apoptotic cell phagocytosis by immature dendritic cells. Significantly, IgM Abs to both PC and MDA were primary factors in determining the efficiency of serum-dependent apoptotic cell phagocytosis. Hence, we demonstrate a mechanism by which certain natural Abs that recognize neoantigens on apoptotic cells, in naive mice and those induced by immune exposure to apoptotic cells, can enhance the functional capabilities of immature dendritic cells for phagocytic engulfment of apoptotic cells.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by the Alliance for Lupus Research, and by Grants AI40305 and AI46637 from the National Institutes of Health–National Institute of Allergy and Infectious Diseases, an Innovative Research Grant from the Arthritis Foundation and funding by the American College of Rheumatology Research and Education Foundation’s Within Our Reach: Finding a Cure for Arthritis campaign (to G.J.S.).

² Address correspondence and reprint requests to Dr. Gregg J. Silverman, Laboratory of B-cell Immunobiology, Department of Medicine, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093. E-mail address: gsilverman{at}ucsd.edu

³ Abbreviations used in this paper: AC, apoptotic cell; C-PS, cell wall polysaccharide; DC, dendritic cell; LDL, low-density lipoprotein; MDA, malondialdehyde; Ox-LDL, oxidized LDL; PC, phosphorylcholine.

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