The role of IgM antibodies in the recognition and clearance of apoptotic cells

Apoptotic cells not only translocate phosphatidylserine to the outside of the membrane, they activate phospholipases that remodel their membranes resulting in the exposure and diffusion of altered phospholipids. These altered phospholipids include lysophosphotidylcholine (LPC) that is a ligand for CRP and is also antigenic for natural IgM antibodies. Furthermore, soluble LPC acts as a “find me” signal to attract phagocytes to migrate toward apoptotic cells. IgM mediated opsonization of apoptotic cells with complement accelerates their clearance by phagocytic cells. Failure to rapidly remove apoptotic cells on the other hand, allows dying cells to undergo post-apoptotic necrosis and inflammation. Natural antibodies therefore provide a previously unrecognized role in prevention of autoimmunity.