调节性树突状细胞通过IFN-β和CD40L调节B细胞分化为CD19 hiFcγIIb hi调节性B细胞

National Key Laboratory of Medical Immunology, Institute of Immunology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China

Regulatory dendritic cells (DCs) play important roles in the induction of peripheral tolerance and control of adaptive immune response. Our previous studies demonstrate that splenic stroma can drive mature DCs to proliferate and further differentiate into a unique subset of CD11b hiIa low regulatory DCs, which could inhibit T-cell response, program generation of immunosuppressive memory CD4 T cells. However, the effect of regulatory DCs on B-cell function remains unclear. Here, we report that regulatory DCs can induce splenic B cells to differentiate into a distinct subtype of IL-10-producing regulatory B cells with unique phenotype CD19 hiFcγIIb hi. CD19 hiFcγIIb hi B cells inhibit CD4 T-cell response via IL-10. CD19 hiFcγIIb hi B cells have enhanced phagocytic capacity compared with conventional CD19 + B cells, and FcγRIIb mediates the uptake of immune complex by CD19 hiFcγIIb hi B cells. We found that regulatory DC-derived IFN-β and CD40 ligand are responsible for the differentiation of CD19 hiFcγIIb hi B cells. Furthermore, an in vivo counterpart of CD19 hiFcγIIb hi B cells in the spleen and lymph nodes with similar phenotype and regulatory function has been identified. Our results demonstrate a new manner for regulatory DCs to down-regulate immune response by, at least partially, programming B cells into regulatory B cells. © 2012 by The American Society of Hematology.

Cao, X.; National Key Laboratory of Medical Immunology, Institute of Immunology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China; email: caoxt@immunol.org