Natural IgM Antibodies Against Oxidation-Specific Epitopes

Natural antibodies (NAbs) are mostly antibodies of the IgM isotype with germline or close to germline encoded variable regions that provide them with specificity for both microbial and altered self antigens. Thus, natural IgM possess an important function in the first line defense against invading pathogens and in tissue homeostasis by regulating the clearance of cellular debris. Oxidation-specific epitopes represent prominent examples of stress-induced altered self, as they are generated ubiquitously as a consequence of lipid peroxidation during many physiological and pathological situations, and are found on the membranes of apoptotic cells. Importantly, oxidation-specific epitopes are dominant targets of natural IgM antibodies, indicating an important role for natural IgM in their clearance and the neutralization of their pro-inflammatory properties. These findings and the insights they provide into the ability of NAbs in mediating host homeostasis in health and diseases, including atherosclerosis and other chronic inflammatory diseases, will be discussed.