B cell activating factor (BAFF) regulates B cell maturation, survival, function, and plays a critical pathogenic role in autoimmune diseases. It remains unclear how BAFF affects IL-10−B cells versus regulatory B cells (Bregs) in inflammatory responses. In this study, we found that IL-10-expressing Bregs decreased in lupus-prone MRL/lpr mice and experimental allergic encephalomyelitis (EAE) mice. On blockade of the effects of BAFF with TACI-IgG, IL-10+ Bregs were upregulated in MRL/lpr and EAE mice. In addition, BAFF expanded IL-10+B cells over IL-10−B cells under noninflammatory conditions in vitro, whereas it expanded IL-10−B cells over IL-10+B cells during inflammatory responses, such as stimulation with autoantigen and LPS. Finally, the selection of IL-10−B cells over IL-10+B cells by BAFF was dependent on BAFF receptors (BAFFR, TACI, and BCMA) that were upregulated by inflammatory responses. This study suggests that BAFF selects IL-10−B cells over IL-10+ regulatory B cells via BAFF receptors in inflammatory responses.