Deficiency of serum immunoglobulin (Ig)M is associated with the development of a lupus-like disease in mice. Recent studies suggest that classical complement components facilitate the clearance of apoptotic cells and that failure to do so predisposes mice to lupus. Since IgM is a potent activator of the classical complement pathway, we examined IgM binding to dying cells. IgM, but not IgG, bound to apoptotic T cells through the Fab′ portion of the antibody. Exposure of apoptotic cell membranes to phospholipase (PL) A2 increased, whereas PLD reduced, IgM binding and complement activation. Absorption studies combined with direct plate binding assays, revealed that IgM antibodies failed to bind to phosphatidyl lipids, but did recognize lysophosphatidylcholine and the phosphorylcholine head group. Both iPLA2 and cPLA2 are activated during apoptosis. Since inhibition of iPLA2, but not cPLA2, attenuated IgM binding to apoptotic cells, these results strongly suggest that the endogenous calcium independent PLA2, iPLA2, is involved in the hydrolysis of plasma membrane phospholipids and exposure of the epitope(s) recognized by IgM. We propose that recognition of dying cells by natural IgM antibodies is, in part, responsible for complement activation on dying cells leading to their safe clearance.
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2 September 2002
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August 26 2002
I-PLA2 Activation during Apoptosis Promotes the Exposure of Membrane Lysophosphatidylcholine Leading to Binding by Natural Immunoglobulin M Antibodies and Complement Activation
Sun Jun Kim,
Sun Jun Kim
1Department of Microbiology & Immunology, Weill Medical College of Cornell University, New York, NY 10021
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Debra Gershov,
Debra Gershov
2Hospital for Special Surgery, Weill Medical College of Cornell University, New York, NY 10021
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Xiaojing Ma,
Xiaojing Ma
1Department of Microbiology & Immunology, Weill Medical College of Cornell University, New York, NY 10021
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Nathan Brot,
Nathan Brot
1Department of Microbiology & Immunology, Weill Medical College of Cornell University, New York, NY 10021
2Hospital for Special Surgery, Weill Medical College of Cornell University, New York, NY 10021
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Keith B. Elkon
Keith B. Elkon
3Division of Rheumatology, University of Washington, Seattle, WA 98195
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Sun Jun Kim
1Department of Microbiology & Immunology, Weill Medical College of Cornell University, New York, NY 10021
Debra Gershov
2Hospital for Special Surgery, Weill Medical College of Cornell University, New York, NY 10021
Xiaojing Ma
1Department of Microbiology & Immunology, Weill Medical College of Cornell University, New York, NY 10021
Nathan Brot
1Department of Microbiology & Immunology, Weill Medical College of Cornell University, New York, NY 10021
2Hospital for Special Surgery, Weill Medical College of Cornell University, New York, NY 10021
Keith B. Elkon
3Division of Rheumatology, University of Washington, Seattle, WA 98195
Address correspondence to Keith Elkon, Division of Rheumatology, Box 356428, University of Washington, Seattle, WA 98195. Phone: 206-543-3414; Fax: 206-685-9397; E-mail: [email protected]
*
Abbreviations used in this paper: BEL, bromoeonol lactone; FPLC, Fast Performance Liquid Chromatography; HGS, hypogammaglobulinemia serum; NHS, normal human serum; MAC, membrane attack complex; PBT, peripheral blood–derived T cell; PC, phosphorylcholine; PE, phosphorylethanolamine; PL, phospholipase; PS, phosphorylserine.
Received:
April 05 2002
Revision Received:
July 16 2002
Accepted:
July 19 2002
Online ISSN: 1540-9538
Print ISSN: 0022-1007
The Rockefeller University Press
2002
J Exp Med (2002) 196 (5): 655–665.
Article history
Received:
April 05 2002
Revision Received:
July 16 2002
Accepted:
July 19 2002
Citation
Sun Jun Kim, Debra Gershov, Xiaojing Ma, Nathan Brot, Keith B. Elkon; I-PLA2 Activation during Apoptosis Promotes the Exposure of Membrane Lysophosphatidylcholine Leading to Binding by Natural Immunoglobulin M Antibodies and Complement Activation . J Exp Med 2 September 2002; 196 (5): 655–665. doi: https://doi.org/10.1084/jem.20020542
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