T-cell-derived signals (CD40L, SAP), cytokines (BAFF, IL-21), and TLRs (especially TLR7), all promote terminal B-cell differentiation by up-regulating the expression of PRDM1. We hypothesize that the enhanced survival of autoreactive B cells in SLE in the setting of BCR engagement and sub-optimal levels of T-cell-derived maturation signals or cytokines may explain the wide diversity of autoantibodies detected in SLE (Figure 2). This evidence concerns the gene PRDM1 and systemic lupus erythematosus.