I-PLA2 Activation during Apoptosis Promotes the Exposure of Membrane Lysophosphatidylcholine Leading to Binding by Natural Immunoglobulin M Antibodies and Complement Activation
Open Access
- 26 August 2002
- journal article
- Published by Rockefeller University Press in The Journal of Experimental Medicine
- Vol. 196 (5), 655-665
- https://doi.org/10.1084/jem.20020542
Abstract
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.This publication has 54 references indexed in Scilit:
- IgG Fc ReceptorsAnnual Review of Immunology, 2001
- Anti-DNA and autoantibodiesCurrent Opinion in Rheumatology, 2000
- Distinct Roles of Two Intracellular Phospholipase A2s in Fatty Acid Release in the Cell Death PathwayPublished by Elsevier BV ,2000
- The Induction of Tolerance by Dendritic Cells That Have Captured Apoptotic CellsThe Journal of Experimental Medicine, 2000
- Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine/paracrine mechanisms involving TGF-beta, PGE2, and PAF.JCI Insight, 1998
- Distinct cleavage products of nuclear proteins in apoptosis and necrosis revealed by autoantibody probesCell Death & Differentiation, 1998
- Oxidative stress as a mediator of apoptosisImmunology Today, 1994
- The Role of Somatic Mutation in the Pathogenic Anti-DNA ResponseAnnual Review of Immunology, 1992
- Normal, Autoimmune, and Malignant CD5+ B Cells: The LY-1 B Lineage?Annual Review of Immunology, 1988
- Rat anti-T15 monoclonal antibodies with specificity for VH− and VH-VL epitopesMolecular Immunology, 1984