Regulatory dendritic cells program B cells to differentiate into CD19hiFcγIIbhi regulatory B cells through IFN-β and CD40L.

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(hi)Ia(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(hi)FcγIIb(hi). CD19(hi)FcγIIb(hi) B cells inhibit CD4 T-cell response via IL-10. CD19(hi)FcγIIb(hi) B cells have enhanced phagocytic capacity compared with conventional CD19(+) B cells, and FcγRIIb mediates the uptake of immune complex by CD19(hi)FcγIIb(hi) B cells. We found that regulatory DC-derived IFN-β and CD40 ligand are responsible for the differentiation of CD19(hi)FcγIIb(hi) B cells. Furthermore, an in vivo counterpart of CD19(hi)FcγIIb(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.