Important questions about pathogenic autoantibodies are whether they arise from germline V genes that contribute to the immunoglobulin repertoire in normal persons, whether they stem from“abnormal”V genes that are peculiar to patients with autoimmune diseases, and whether they are encoded by unmodified or somatically mutated immunoglobulin genes. These issues influence the way we think about three aspects of autoimmunity: genetic susceptibility to autoimmunization, the origins of lesion-producing autoantibodies, and the prevention and medical management of autoimmune disorders.