IFN-α-producing PDCA-1+Siglec-H- B cells mediate innate immune defense by activating NK cells

B cells have multiple functions in adaptive immunity, including antibody production, antigen presentation and regulation of T-cell responses. Recent evidences indicate that B cells have more subsets than previously thought and may have non-classical functions, such as involvement in innate immunity and immune regulation; however, how B cells respond to microbial infection and elicit innate defense remain unclear. In this study, we identified a new subset of PDCA-1(+)Siglec-H- CD19(+) B cells in mice during the early period of bacterial infection with Listeria monocytogenes. PDCA-1(+)Siglec-H- CD19(+) B cells secreted large amounts of IFN-alpha and thus facilitated IFN-gamma production and cytotoxicity function of natural killer (NK) cells via IFN-alpha. B-cell-deficient Btk(-/-) mice were incapable of producing PDCA-1(+)CD19(+) B cells, and were more sensitive to L. monocytogenes infection. Adoptive transfer of PDCA-1(+)CD19(+) B cells to Btk(-/-) mice normalized their resistance to L. monocytogenes infection. Furthermore, we found that macrophages were essential for the inducible generation of PDCA-1(+)Siglec-H(-)CD19(+) B cells via CD40-CD40L ligation. Therefore, we have identified a new subset of PDCA-1(+)Siglec-H(-)CD19(+) B cells, which enhances innate immune responses against bacterial infection by activating NK cells via secretion of IFN-alpha.