A Regulatory Role for IL-10 Receptor Signaling in Development and B Cell Help of T Follicular Helper Cells in Mice

IL-10 is widely accepted as a survival, proliferation, and differentiation factor for B cells. However, IL-10 deficiency accelerates disease progression as the result of autoantibody production in many autoimmune disease models. It was demonstrated that T follicular helper cells (T-FH cells) play a key role in helping B cells that are secreting Abs. In this study, we demonstrated a regulatory role for IL-10R signaling on the development and B cell help function of T-FH cells in vitro and in vivo. IL-1R subunit beta-deficient (Il10rb(-/-)) Th cells were able to differentiate more readily into TFH cells, as well as secrete more IL-21 and IL-17 compared with wild-type Th cell-derived T-FH cells. Increased IL-21 and IL-17 contributed to the enhanced B cell help functions of T-FH cells. Further experiments demonstrated that IL-6 and IL-23 from dendritic cells in IlL0rb(-/-) mice contributed to the differentiation of naive Th cells into T-FH cells, as well as the generation of IL-21-and IL-17-producing T-FH cells. Our results provide useful information for clarifying the immunoregulatory mechanisms associated with IL-10 deficiency in certain autoimmune disease models. This information could also be of benefit for the development of vaccines. The Journal of Immunology, 2012, 189: 1294-1302.