title: Diversity of gut microflora is required for the generation of B cell with regulatory properties in a skin graft model.
abstract: B cells have been reported to promote graft rejection through alloantibody production. However, there is growing evidence that B cells can contribute to the maintenance of tolerance. Here, we used a mouse model of MHC-class I mismatched skin transplantation to investigate the contribution of B cells to graft survival. We demonstrate that adoptive transfer of B cells prolongs skin graft survival but only when the B cells were isolated from mice housed in low sterility "conventional" (CV) facilities and not from mice housed in pathogen free facilities (SPF). However, prolongation of skin graft survival was lost when B cells were isolated from IL-10 deficient mice housed in CV facilities. The suppressive function of B cells isolated from mice housed in CV facilities correlated with an anti-inflammatory environment and with the presence of a different gut microflora compared to mice maintained in SPF facilities. Treatment of mice in the CV facility with antibiotics abrogated the regulatory capacity of B cells. Finally, we identified transitional B cells isolated from CV facilities as possessing the regulatory function. These findings demonstrate that B cells, and in particular transitional B cells, can promote prolongation of graft survival, a function dependent on licensing by gut microflora.
authors.affiliation: Medical Research Council Centre for Transplantation, King's College London, King's Health Partners, Guy's Hospital, London SE1 9RT, UK.
authors.forename: R
authors.initials: R
authors.lastname: Alhabbab
authors.affiliation: Medical Research Council Centre for Transplantation, King's College London, King's Health Partners, Guy's Hospital, London SE1 9RT, UK.
authors.forename: P
authors.initials: P
authors.lastname: Blair
authors.affiliation: Medical Research Council Centre for Transplantation, King's College London, King's Health Partners, Guy's Hospital, London SE1 9RT, UK.
authors.forename: R
authors.initials: R
authors.lastname: Elgueta
authors.affiliation: Division of Diabetes and Nutritional Sciences, King's College London, Guy's Hospital, London SE1 9RT, UK.
authors.forename: E
authors.initials: E
authors.lastname: Stolarczyk
authors.affiliation: Medical Research Council Centre for Transplantation, King's College London, King's Health Partners, Guy's Hospital, London SE1 9RT, UK.
authors.forename: E
authors.initials: E
authors.lastname: Marks
authors.affiliation: Medical Research Council Centre for Transplantation, King's College London, King's Health Partners, Guy's Hospital, London SE1 9RT, UK.
authors.forename: P D
authors.initials: PD
authors.lastname: Becker
authors.affiliation: Medical Research Council Centre for Transplantation, King's College London, King's Health Partners, Guy's Hospital, London SE1 9RT, UK.
authors.forename: K
authors.initials: K
authors.lastname: Ratnasothy
authors.affiliation: Medical Research Council Centre for Transplantation, King's College London, King's Health Partners, Guy's Hospital, London SE1 9RT, UK.
authors.forename: L
authors.initials: L
authors.lastname: Smyth
authors.affiliation: Medical Research Council Centre for Transplantation, King's College London, King's Health Partners, Guy's Hospital, London SE1 9RT, UK.
authors.forename: N
authors.initials: N
authors.lastname: Safinia
authors.affiliation: Medical Research Council Centre for Transplantation, King's College London, King's Health Partners, Guy's Hospital, London SE1 9RT, UK.
authors.forename: E
authors.initials: E
authors.lastname: Sharif-Paghaleh
authors.affiliation: Medical Research Council Centre for Transplantation, King's College London, King's Health Partners, Guy's Hospital, London SE1 9RT, UK.
authors.forename: S
authors.initials: S
authors.lastname: O'Connell
authors.affiliation: Medical Research Council Centre for Transplantation, King's College London, King's Health Partners, Guy's Hospital, London SE1 9RT, UK.
authors.forename: R J
authors.initials: RJ
authors.lastname: Noelle
authors.affiliation: Medical Research Council Centre for Transplantation, King's College London, King's Health Partners, Guy's Hospital, London SE1 9RT, UK.
authors.forename: G M
authors.initials: GM
authors.lastname: Lord
authors.affiliation: Division of Diabetes and Nutritional Sciences, King's College London, Guy's Hospital, London SE1 9RT, UK.
authors.forename: J K
authors.initials: JK
authors.lastname: Howard
authors.affiliation: Peter Gorer Department of Immunobiology, King's College London, Guy's Hospital, London SE1 9RT, UK.
authors.forename: J
authors.initials: J
authors.lastname: Spencer
authors.affiliation: Medical Research Council Centre for Transplantation, King's College London, King's Health Partners, Guy's Hospital, London SE1 9RT, UK.
authors.forename: R I
authors.initials: RI
authors.lastname: Lechler
authors.affiliation: Medical Research Council Centre for Transplantation, King's College London, King's Health Partners, Guy's Hospital, London SE1 9RT, UK.
authors.forename: G
authors.initials: G
authors.lastname: Lombardi
mesh_terms: D056704:Adaptive Immunity; D019264:Adoptive Transfer; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001402:B-Lymphocytes / Q000166:cytology / Q000201:enzymology / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D000069196:Gastrointestinal Microbiome / Q000187:drug effects; D006085:Graft Survival / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism; D007108:Immune Tolerance; D016753:Interleukin-10 / Q000172:deficiency / Q000235:genetics; D008070:Lipopolysaccharides / Q000633:toxicity; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016038:Skin Transplantation; D013154:Spleen / Q000276:immunology / Q000473:pathology; D014184:Transplantation, Homologous
chemical_list: D000900:Anti-Bacterial Agents; D016207:Cytokines; D015395:Histocompatibility Antigens Class I; D008070:Lipopolysaccharides; D016753:Interleukin-10