title: Identification of IFN-γ-producing innate B cells.
abstract: Although B cells play important roles in the humoral immune response and the regulation of adaptive immunity, B cell subpopulations with unique phenotypes, particularly those with non-classical immune functions, should be further investigated. By challenging mice with Listeria monocytogenes, Escherichia coli, vesicular stomatitis virus and Toll-like receptor ligands, we identified an inducible CD11a(hi)FcγRIII(hi) B cell subpopulation that is significantly expanded and produces high levels of IFN-γ during the early stage of the immune response. This subpopulation of B cells can promote macrophage activation via generating IFN-γ, thereby facilitating the innate immune response against intracellular bacterial infection. As this new subpopulation is of B cell origin and exhibits the phenotypic characteristics of B cells, we designated these cells as IFN-γ-producing innate B cells. Dendritic cells were essential for the inducible generation of these innate B cells from the follicular B cells via CD40L-CD40 ligation. Increased Bruton's tyrosine kinase activation was found to be responsible for the increased activation of non-canonical NF-κB pathway in these innate B cells after CD40 ligation, with the consequent induction of additional IFN-γ production. The identification of this new population of innate B cells may contribute to a better understanding of B cell functions in anti-infection immune responses and immune regulation.
authors.affiliation: 1] Translational Medicine Center, Changzheng Hospital, Second Military Medical University, Shanghai 200433, China [2] National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University, Shanghai 200433, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Bao
authors.affiliation: National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University, Shanghai 200433, China.
authors.forename: Xingguang
authors.initials: X
authors.lastname: Liu
authors.affiliation: National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University, Shanghai 200433, China.
authors.forename: Chaofeng
authors.initials: C
authors.lastname: Han
authors.affiliation: National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University, Shanghai 200433, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Xu
authors.affiliation: National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University, Shanghai 200433, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Xie
authors.affiliation: National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University, Shanghai 200433, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University, Shanghai 200433, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Gu
authors.affiliation: National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University, Shanghai 200433, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Hou
authors.affiliation: National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University, Shanghai 200433, China.
authors.forename: Li
authors.initials: L
authors.lastname: Qian
authors.affiliation: National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University, Shanghai 200433, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Qian
authors.affiliation: Translational Medicine Center, Changzheng Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Huanxing
authors.initials: H
authors.lastname: Han
authors.affiliation: National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University, Shanghai 200433, China.
authors.forename: Xuetao
authors.initials: X
authors.lastname: Cao
mesh_terms: D000077329:Agammaglobulinaemia Tyrosine Kinase; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000166:cytology; D040881:CD11a Antigen / Q000378:metabolism; D019013:CD40 Antigens / Q000378:metabolism; D023201:CD40 Ligand / Q000378:metabolism; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008089:Listeria monocytogenes / Q000472:pathogenicity; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D017452:Receptors, IgG / Q000378:metabolism
chemical_list: D040881:CD11a Antigen; D019013:CD40 Antigens; C485700:Fcgr3 protein, mouse; D016328:NF-kappa B; D017452:Receptors, IgG; D023201:CD40 Ligand; D007371:Interferon-gamma; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625951:Btk protein, mouse