title: Marginal zone B cells exacerbate endotoxic shock via interleukin-6 secretion induced by Fcα/μR-coupled TLR4 signalling.
abstract: Marginal zone (MZ) B cells produce a first wave of antibodies for protection from blood-borne pathogens. However, the role of MZ B cells in inflammatory responses has not been elucidated. Here we show that MZ B cells produce pro-inflammatory cytokines, such as interleukin-6 (IL-6), and exacerbate systemic inflammatory responses to lipopolysaccharide (LPS). After intravenous injection of LPS or E. coli, mice deficient in MZ B cells or IL-6 only in MZ B cells have attenuated systemic inflammatory responses and prolonged survival compared with wild-type mice. LPS directly stimulates MZ B cells via Toll-like receptor 4 (TLR4) and MyD88 pathways for IL-6 production. Furthermore, TLR4 requires physical and functional association with Fcα/μR (CD351) for its oligomer formation, NF-κB signalling and IL-6 production from MZ B cells; this association is responsible for systemic inflammatory responses and endotoxic shock. These results reveal a pro-inflammatory role of MZ B cells in endotoxic shock.
authors.affiliation: Department of Immunology, Faculty of Medicine, University of Tsukuba, 1-1-1, Tennohdai, Tsukuba 305-8575, Ibaraki, Japan.
authors.forename: Shin-Ichiro
authors.initials: S
authors.lastname: Honda
authors.affiliation: Department of Immunology, Faculty of Medicine, University of Tsukuba, 1-1-1, Tennohdai, Tsukuba 305-8575, Ibaraki, Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Sato
authors.affiliation: Department of Immunology, Faculty of Medicine, University of Tsukuba, 1-1-1, Tennohdai, Tsukuba 305-8575, Ibaraki, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Totsuka
authors.affiliation: Department of Immunology, Faculty of Medicine, University of Tsukuba, 1-1-1, Tennohdai, Tsukuba 305-8575, Ibaraki, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Fujiyama
authors.affiliation: Department of Dermatology, Faculty of Medicine, University of Tsukuba, 1-1-1, Tennohdai, Tsukuba 305-8575, Ibaraki, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Fujimoto
authors.affiliation: Division of Innate Immunity, Institute of Medical Sciences, University of Tokyo, Shirokanedai, Minatoloku, Tokyo 108-8639, Japan.
authors.forename: Kensuke
authors.initials: K
authors.lastname: Miyake
authors.affiliation: Department of Immunology, Faculty of Medicine, University of Tsukuba, 1-1-1, Tennohdai, Tsukuba 305-8575, Ibaraki, Japan.
authors.forename: Chigusa
authors.initials: C
authors.lastname: Nakahashi-Oda
authors.affiliation: Department of Immunology, Faculty of Medicine, University of Tsukuba, 1-1-1, Tennohdai, Tsukuba 305-8575, Ibaraki, Japan.|Life Science Center of Tsukuba Advanced Research Alliance (TARA), University of Tsukuba, 1-1-1, Tennohdai, Tsukuba 305-8575, Ibaraki, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Tahara-Hanaoka
authors.affiliation: Department of Immunology, Faculty of Medicine, University of Tsukuba, 1-1-1, Tennohdai, Tsukuba 305-8575, Ibaraki, Japan.
authors.forename: Kazuko
authors.initials: K
authors.lastname: Shibuya
authors.affiliation: Department of Immunology, Faculty of Medicine, University of Tsukuba, 1-1-1, Tennohdai, Tsukuba 305-8575, Ibaraki, Japan.|Life Science Center of Tsukuba Advanced Research Alliance (TARA), University of Tsukuba, 1-1-1, Tennohdai, Tsukuba 305-8575, Ibaraki, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Shibuya
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism*; D004927:Escherichia coli Infections / Q000503:physiopathology; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D011961:Receptors, Fc / Q000235:genetics / Q000378:metabolism*; D012772:Shock, Septic / Q000503:physiopathology; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*
chemical_list: C526791:Fcalpha-mu protein, mouse; D015850:Interleukin-6; D008070:Lipopolysaccharides; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D011961:Receptors, Fc; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4