Naturally occurring autoantibodies to apoptotic cells.

Subsets of IgM naturally occurring autoantibodies (NAbs) bind to the cell surface membranes of dying cells. The antibodies predominantly have specificities against lipid antigens or oxidized lipids. Chief among these lipid antigens are phosphorylcholine (PC) and malondialdehyde (MDA). Antibodies to negatively charged phospholipids such as phosphatidylserine (PS) have been described and there is controversy as to whether these antibodies are related to anticardiolipin antibodies observed in disease states. IgM NAbs that bind to apoptotic cells recruit classical complement pathway components and facilitate phagocytosis by both macrophages and dendritic cells, and may block inflammatory pathways. Under these circumstances, pathologic immune responses to self (autoimmunity) are avoided, whereas mice lacking serum IgM develop a lupus-like disease with associated IgG autoantibody responses. Based on these observations, IgM anti-PC NAbs were found to attenuate inflammation in mouse models of arthritis. IgMNAbs antibodies therefore appear to play pivotal roles in the dampening inflammation and maintenance of tolerance.