Apoptotic and necrotic cells are strong candidates as sources of the autoantigens that drive the autoantibody response in systemic lupus erythematosus (SLE). Defects in the physiological mechanisms for the clearance of dying cells may promote disease susceptibility to SLE. Ablation of the mouse gene Dnase1 results in the development of anti-chromatin autoimmunity and glomerulonephritis, indicating that the enzyme protects against autoimmunity by digesting extracellular chromatin.

The autoimmune disease SLE is characterized by a peculiar spectrum of autoantibodies. Their respective antigens are abundant in every cell of the body and include chromatin, ribonucleoprotein components of the spliceosome complex, and phospholipid components of the cell membrane, such as phosphatidylserine. It is essential to understand how the autoantigens driving the pathogenic autoimmune are selected in order to understand the aetiology of SLE. A study presented on page 177 of this issue, by Tarik Möröy and colleagues, confirms the identity of a player that may contribute to the predominance of anti-chromatin and anti-DNA autoantibodies in the autoimmune response. For many years, researchers focused on analysing the autoantibodies and their pattern of autoantibody recognition. There are two important outcomes of this work. First, the autoantibody response shows every sign of being mediated by an antigen-driven, T-cell–dependent mechanism. Autoantibodies are usually polyclonal, of the immunoglobulin G class and