title: Thymic B cells promote thymus-derived regulatory T cell development and proliferation.
abstract: Thymic CD4(+) FoxP3(+) regulatory T (Treg) cells are critical for the development of immunological tolerance and immune homeostasis and requires contributions of both thymic dendritic and epithelial cells. Although B cells have been reported to be present within the thymus, there has not hitherto been a definition of their role in immune cell development and, in particular, whether or how they contribute to the Treg cellular thymic compartment. Herein, using both phenotypic and functional approaches, we demonstrate that thymic B cells contribute to the maintenance of thymic Treg cells and, using an in vitro culture system, demonstrate that thymic B cells contribute to the size of the thymic Treg compartment via cell-cell MHC II contact and the involvement of two independent co-stimulatory pathways that include interactions between the CD40/CD80/CD86 co-stimulatory molecules. Our data also suggest that thymic B cells promote the generation of thymic Treg cell precursors (pre-Treg cells), but not the conversion of FoxP3(+) Treg cells from pre-Treg cells. In addition, thymic B cells directly promote the proliferation of thymic Treg cells that is MHC II contact dependent with a minimal if any role for co-stimulatory molecules including CD40/CD80/CD86. Both pathways are independent of TGFβ. In conclusion, we rigorously define the critical role of thymic B cells in the development of thymic Treg cells from non-Treg to precursor stage and in the proliferation of mature thymic Treg cells.
authors.affiliation: Liver Immunology Laboratory, Institute of Immunology and The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027, China. Electronic address: fangting@mail.ustc.edu.cn.
authors.forename: Fang-Ting
authors.initials: FT
authors.lastname: Lu
authors.affiliation: Liver Immunology Laboratory, Institute of Immunology and The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027, China. Electronic address: ywei0702@mail.ustc.edu.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Yang
authors.affiliation: Liver Immunology Laboratory, Institute of Immunology and The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027, China. Electronic address: wangyh8@mail.ustc.edu.cn.
authors.forename: Yin-Hu
authors.initials: YH
authors.lastname: Wang
authors.affiliation: Liver Immunology Laboratory, Institute of Immunology and The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027, China. Electronic address: mahongdi@ustc.edu.cn.
authors.forename: Hong-Di
authors.initials: HD
authors.lastname: Ma
authors.affiliation: Liver Immunology Laboratory, Institute of Immunology and The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027, China. Electronic address: wayne012@mail.ustc.edu.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Tang
authors.affiliation: Liver Immunology Laboratory, Institute of Immunology and The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027, China. Electronic address: yjingb@mail.ustc.edu.cn.
authors.forename: Jing-Bo
authors.initials: JB
authors.lastname: Yang
authors.affiliation: Liver Immunology Laboratory, Institute of Immunology and The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027, China. Electronic address: lil2009@mail.ustc.edu.cn.
authors.forename: Liang
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Pathology, Emory University School of Medicine, Atlanta, GA 30322, USA. Electronic address: pathaaa@emory.edu.
authors.forename: Aftab A
authors.initials: AA
authors.lastname: Ansari
authors.affiliation: Liver Immunology Laboratory, Institute of Immunology and The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences and Medical Center, University of Science and Technology of China, Hefei, Anhui 230027, China; Innovation Center for Cell Signaling Network, Hefei National Laboratory for Physical Sciences at Microscale, Hefei, Anhui 230026, China. Electronic address: zxlian1@ustc.edu.cn.
authors.forename: Zhe-Xiong
authors.initials: ZX
authors.lastname: Lian
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018122:B7-1 Antigen / Q000276:immunology; D051940:B7-2 Antigen / Q000276:immunology; D019013:CD40 Antigens / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D005434:Flow Cytometry; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006706:Homeostasis / Q000276:immunology; D007108:Immune Tolerance / Q000276:immunology; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D013950:Thymus Gland / Q000276:immunology*
chemical_list: D018122:B7-1 Antigen; D051940:B7-2 Antigen; D019013:CD40 Antigens; D000949:Histocompatibility Antigens Class II
keywords: Cell–cell contact; Development; Proliferation; Thymic B cells; Thymic Treg cells