Abstract: Antibodies are protective effector molecules in the body's immune defense against pathogens. However, if directed against the body's own tissues or organs, antibodies can also play a role in the pathogenesis of autoimmune disease. Here, we discuss our data on how autoreactive antibodies are regulated in healthy humans and how a failure to establish self‐tolerance during early B‐cell development in patients with systemic lupus erythematosus may predispose to the development of this autoimmune disease.