title: Regulatory B cells are induced by gut microbiota-driven interleukin-1β and interleukin-6 production.
abstract: Regulatory B cells (Breg cells) differentiate in response to inflammation and subsequently restrain excessive immune responses via the release of interleukin-10 (IL-10). However, the precise inflammatory signals governing their differentiation remain to be elucidated. Here we show that the gut microbiota promotes the differentiation of Breg cells in the spleen as well as in the mesenteric lymph nodes. Perturbation of the gut microbiome imposed either by antibiotic treatment or by changes in the sterility of housing conditions reduces the number and function of Breg cells. Following the induction of arthritis, IL-1β and IL-6 are produced only in conventionally housed mice and both cytokines directly promote Breg cell differentiation and IL-10 production. Mice lacking IL-6 receptor (IL-6R) or IL-1 receptor 1 (IL-1R1) specifically on B cells have a reduced number of IL-10-producing B cells and develop exacerbated arthritis compared to control animals. Thus, in response to inflammatory signals induced by both the gut flora and arthritis, Breg cells increase in number and restrain excessive inflammation.
authors.affiliation: Centre for Rheumatology, Division of Medicine, University College London, London, UK.
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Rosser
authors.affiliation: Centre for Rheumatology, Division of Medicine, University College London, London, UK.
authors.forename: Kristine
authors.initials: K
authors.lastname: Oleinika
authors.affiliation: Universita' degli Studi di Udine, Dipartimento di Medicina e Scienze Biologiche, Udine, Italia.
authors.forename: Silvia
authors.initials: S
authors.lastname: Tonon
authors.affiliation: Infectious Diseases and Microbiology Unit, Institute of Child Health, University College London, London, UK.
authors.forename: Ronan
authors.initials: R
authors.lastname: Doyle
authors.affiliation: Centre for Rheumatology, Division of Medicine, University College London, London, UK.
authors.forename: Anneleen
authors.initials: A
authors.lastname: Bosma
authors.affiliation: Centre for Rheumatology, Division of Medicine, University College London, London, UK.
authors.forename: Natalie A
authors.initials: NA
authors.lastname: Carter
authors.affiliation: Department of Microbiology, Virology and Infection Control, Great Ormond Street Hospital National Health Service Foundation Trust, London, UK.
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Harris
authors.affiliation: Cardiff Institute for Infection &Immunity, The School of Medicine, Cardiff University, Cardiff, Wales, UK.
authors.forename: Simon A
authors.initials: SA
authors.lastname: Jones
authors.affiliation: Infectious Diseases and Microbiology Unit, Institute of Child Health, University College London, London, UK.
authors.forename: Nigel
authors.initials: N
authors.lastname: Klein
authors.affiliation: Centre for Rheumatology, Division of Medicine, University College London, London, UK.
authors.forename: Claudia
authors.initials: C
authors.lastname: Mauri
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001169:Arthritis, Experimental / Q000276:immunology / Q000473:pathology; D060151:B-Lymphocytes, Regulatory / Q000187:drug effects / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D005434:Flow Cytometry; D041981:Gastrointestinal Tract / Q000187:drug effects / Q000382:microbiology*; D007249:Inflammation / Q000473:pathology; D016753:Interleukin-10 / Q000096:biosynthesis; D053583:Interleukin-1beta / Q000096:biosynthesis*; D015850:Interleukin-6 / Q000096:biosynthesis*; D008198:Lymph Nodes / Q000187:drug effects / Q000378:metabolism; D008810:Mice, Inbred C57BL; D064307:Microbiota / Q000187:drug effects; D013047:Specific Pathogen-Free Organisms
chemical_list: D000900:Anti-Bacterial Agents; D053583:Interleukin-1beta; D015850:Interleukin-6; D016753:Interleukin-10