The Journal of Experimental Medicine
VeriKine-HS Human IFN-Beta
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Published online 26 August 2002 doi:10.1084/jem.20020542
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© Rockefeller University Press, 0022-1007/2002/9/655/ $5.00
The Journal of Experimental Medicine, Volume 196, Number 5, September 2, 2002 655-665

I-PLA2 Activation during Apoptosis Promotes the Exposure of Membrane Lysophosphatidylcholine Leading to Binding by Natural Immunoglobulin M Antibodies and Complement Activation

Sun Jun Kim1, Debra Gershov2, Xiaojing Ma1, Nathan Brot1,2 and Keith B. Elkon3

1 Department of Microbiology & Immunology, Weill Medical College of Cornell University, New York, NY 10021
2 Hospital for Special Surgery, Weill Medical College of Cornell University, New York, NY 10021
3 Division 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: elkon{at}u.washington.edu

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.

Key Words: IgM • apoptosis • complement • macrophages • autoimmunity


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