Identification of a human monoclonal natural IgM antibody that recognizes early apoptotic cells and promotes phagocytosis.

Efficient clearance of cells undergoing apoptotic death is crucial for normal tissue homeostasis and for the prevention of autoimmunity. Engulfment of apoptotic cells is finely regulated by a highly redundant system of receptors and bridging molecules. We developed a rapid and efficient method for the identification of human natural IgM antibodies and isolated some natural human monoclonal IgM antibodies specific to the apoptotic cells. Among them, AC34 IgM bound to early apoptotic cells and promoted phagocytosis of apoptotic Jurkat cells by human monocyte-derived macrophage (HMDM). AC34 IgM recognized phosphatidylserine (PS), which means PS might be a possible molecule recognized by AC34 IgM on the surface of apoptotic cells and AC34 IgM might be a possible candidate of bridging molecules between the PS and phagocytes. The sequences of V(H) and V(L) of AC34 were almost the same with their germline counterpart. Our experiments suggest a role of natural IgM as an opsonin in the clearance of early apoptotic cells.