The tangled web of autoreactive B cells in malaria immunity and autoimmune disease

Two seminal observations suggest that the African genome contains genes selected by malaria that protect against systemic lupus erythematosus (SLE) in individuals chronically exposed to malaria, but which in the absence of malaria, are risk factors for SLE. First, Brian Greenwood observed that SLE was rare in Africa and that malaria prevented SLE-like disease in susceptible mice. Second, African-Americans, as compared with individuals of European descent, are at higher risk of SLE. Understanding that antibodies play central roles in malaria immunity and SLE, we discuss how autoreactive B cells contribute to malaria immunity but promote SLE pathology in the absence of malaria. Testing this model may provide insights into the regulation of autoreactivity and identify new therapeutic targets for SLE.