title: IFN-α-producing PDCA-1+ Siglec-H- B cells mediate innate immune defense by activating NK cells.
abstract: 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-α and thus facilitated IFN-γ production and cytotoxicity function of natural killer (NK) cells via IFN-α. 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-α.
authors.affiliation: National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University, Shanghai, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Bao
authors.forename: Yanmei
authors.initials: Y
authors.lastname: Han
authors.forename: Zhubo
authors.initials: Z
authors.lastname: Chen
authors.forename: Sheng
authors.initials: S
authors.lastname: Xu
authors.forename: Xuetao
authors.initials: X
authors.lastname: Cao
mesh_terms: D019264:Adoptive Transfer; D000077329:Agammaglobulinaemia Tyrosine Kinase; D000818:Animals; D018941:Antigens, CD19 / Q000378:metabolism; D000943:Antigens, Differentiation / Q000378:metabolism; D016175:B-Lymphocyte Subsets / Q000201:enzymology / Q000276:immunology*; D001483:Base Sequence; D019013:CD40 Antigens / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D023201:CD40 Ligand / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D007113:Immunity, Innate; D066298:In Vitro Techniques; D016898:Interferon-alpha / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics; D007371:Interferon-gamma / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics; D007694:Killer Cells, Natural / Q000276:immunology*; D037102:Lectins / Q000378:metabolism; D008088:Listeriosis / Q000201:enzymology / Q000276:immunology; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011505:Protein-Tyrosine Kinases / Q000172:deficiency / Q000235:genetics; D011956:Receptors, Cell Surface / Q000378:metabolism
chemical_list: D018941:Antigens, CD19; D000943:Antigens, Differentiation; D019013:CD40 Antigens; D017931:DNA Primers; D016898:Interferon-alpha; D037102:Lectins; D011956:Receptors, Cell Surface; C510552:Siglech protein, mouse; D023201:CD40 Ligand; D007371:Interferon-gamma; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase