title: Naive B cells generate regulatory T cells in the presence of a mature immunologic synapse.
abstract: Naive B cells are ineffective antigen-presenting cells and are considered unable to activate naive T cells. However, antigen-specific contact of these cells leads to stable cell pairs that remain associated over hours in vivo. The physiologic role of such pairs has not been evaluated. We show here that antigen-specific conjugates between naive B cells and naive T cells display a mature immunologic synapse in the contact zone that is absent in T-cell-dendritic-cell (DC) pairs. B cells induce substantial proliferation but, contrary to DCs, no loss of L-selectin in T cells. Surprisingly, while DC-triggered T cells develop into normal effector cells, B-cell stimulation over 72 hours induces regulatory T cells inhibiting priming of fresh T cells in a contact-dependent manner in vitro. In vivo, the regulatory T cells home to lymph nodes where they potently suppress immune responses such as in cutaneous hypersensitivity and ectopic allogeneic heart transplant rejection. Our finding might help to explain old observations on tolerance induction by B cells, identify the mature immunologic synapse as a central functional module of this process, and suggest the use of naive B-cell-primed regulatory T cells, "bTregs," as a useful approach for therapeutic intervention in adverse adaptive immune responses.
authors: Helmholtz Centre for Infection Research (HZI), Junior Research Group Immunodynamics, Braunschweig, Germany.
authors: Peter
authors: P
authors: Reichardt
authors: Bastian
authors: B
authors: Dornbach
authors: Song
authors: S
authors: Rong
authors: Stefan
authors: S
authors: Beissert
authors: Faikah
authors: F
authors: Gueler
authors: Karin
authors: K
authors: Loser
authors: Matthias
authors: M
authors: Gunzer
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000941:Antigens / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology; D003876:Dermatitis, Atopic / Q000276:immunology* / Q000628:therapy; D006084:Graft Rejection / Q000276:immunology* / Q000628:therapy; D016027:Heart Transplantation / Q000502:physiology*; D019041:L-Selectin / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D050378:T-Lymphocytes, Regulatory; D023001:Transplantation Tolerance / Q000276:immunology*; D014184:Transplantation, Homologous
chemical_list: D000941:Antigens; D019041:L-Selectin