These data suggest that Tfh cell-derived IL-21 may induce the production of the anti-inflammatory cytokine IL-10 and result in expansion of Breg cells in SLE. Thus, the pathophysiology of SLE may be linked to a complex immune relationship between Tfh cells and diverse B subsets. The percentage of Breg cells was expanded in SLE patients and decreased following remission than in healthy controls, these data suggested that Breg cells are dynamic during the development of autoimmunity. Maintaining immunological balance involves the capacity of the immune system to upregulate immunosuppressive responses, which may limit deterioration by the autoimmune response. The upregulation of Breg cells in FG-4592 active SLE patients may reflect a regulatory feedback mechanism to restore cellular tolerance and ameliorate harmful autoimmune responses. B10 cells were functionally identified by their ability to express cytoplasmic IL-10 after 5 hours of ex vivo stimulation, whereas progenitor B10 cells required 48 hours of in vitro stimulation before they acquired the ability to express IL-10. Recent study showed that the percentages of B10 cells in SLE patients were not significantly different from controls, but the percentages of B10+Bpro cells in SLE patients were significantly different from controls, these data implied that B cells in SLE have more potential to produce IL-10. In our study, modified methods were taken, the B cells were stimulated with LPS 24 hours and the last 5 hours of PIB stimulation, which was based on the previous reported methods. Consistent with previous results, our study confirmed that both IL-10 production and the percentage of CD19+ IL-10+ B cells were increased in SLE patients; however, the reason behind this expansion of Breg cells in SLE was not addressed in the previous studies. Our data showed that the absolute numbers of CD4+ CXCR5+ PD-1+ Tfh cells were not significantly increased in SLE patients than in healthy controls, however the percentage of CD4+ CXCR5+ PD-1+ Tfh cells were expanded in active SLE patients and that Tfh cellderived IL-21 contributed to autoantibody production.Which suggested that Tfh cells may contribute to autoimmunity by helping B effector cells and inducing humoral immunity. Secondly, we unexpectedly identified a strong positive correlation between Tfh cells and Breg cells in SLE patients, suggesting that Tfh cells may contribute to the expansion of Breg cells in SLE. Our in vitro data further revealed that SLE patient Tfh cell-derived IL-21 in synergy with LPS and PI promoted IL-10 production and the differentiation of Breg cells. This finding was verified as treatment of these cultures with an IL-21-neutralizing antibody inhibited IL-10 production and the generation of CD19+ IL-10+ cells. IL-21 is a pleiotropic cytokine, and at least under certain circumstances, IL-21 can stimulate anti-inflammatory IL-10 production in T and B cells.