The pathophysiological relevance of B cells for systemic lupus erythematosus (SLE), particularly those expressing the T-cell marker CD5, raises the question as to how they operate upon autoimmune processes. Based on their production of low-affinity multispecific antibodies (Abs), CD5(+) B lymphocytes, also referred to as B1 cells, have originally been endowed with the autoAb making. It has since been established that high-affinity Abs to double-stranded DNA are not generated by these cells, but rather by B2 cells. It does not appear that they have the exclusive rights to the production of pathogenic autoAbs. In the light of recent findings, CD5 plays a paradoxical role in preventing autoimmunity. Hence, misguided signaling through CD5 could lead to autoimmunity. This provocative view differs from the naïve interpretation that the increased levels of B1 cells in SLE represent a direct source of autoAbs responsible for damaging organs.