title: Treatment of ongoing autoimmune encephalomyelitis with activated B-cell progenitors maturing into regulatory B cells.
abstract: The influence of signals perceived by immature B cells during their development in bone marrow on their subsequent functions as mature cells are poorly defined. Here, we show that bone marrow cells transiently stimulated in vivo or in vitro through the Toll-like receptor 9 generate proB cells (CpG-proBs) that interrupt experimental autoimmune encephalomyelitis (EAE) when transferred at the onset of clinical symptoms. Protection requires differentiation of CpG-proBs into mature B cells that home to reactive lymph nodes, where they trap T cells by releasing the CCR7 ligand, CCL19, and to inflamed central nervous system, where they locally limit immunopathogenesis through interleukin-10 production, thereby cooperatively inhibiting ongoing EAE. These data demonstrate that a transient inflammation at the environment, where proB cells develop, is sufficient to confer regulatory functions onto their mature B-cell progeny. In addition, these properties of CpG-proBs open interesting perspectives for cell therapy of autoimmune diseases.
authors.affiliation: Institut Necker Enfants Malades, Immunology, Infectiology and Haematology Department, Inserm U1151, CNRS UMR 8253, 14 rue Maria Helena Vieira da Silva, CS 61431, Paris 75014, France.|Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine Site Necker, 14 rue Maria Helena Vieira da Silva, CS 61431, Paris 75014, France.
authors.forename: Sarantis
authors.initials: S
authors.lastname: Korniotis
authors.affiliation: Institut Necker Enfants Malades, Immunology, Infectiology and Haematology Department, Inserm U1151, CNRS UMR 8253, 14 rue Maria Helena Vieira da Silva, CS 61431, Paris 75014, France.|Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine Site Necker, 14 rue Maria Helena Vieira da Silva, CS 61431, Paris 75014, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Gras
authors.affiliation: Institut Necker Enfants Malades, Immunology, Infectiology and Haematology Department, Inserm U1151, CNRS UMR 8253, 14 rue Maria Helena Vieira da Silva, CS 61431, Paris 75014, France.|Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine Site Necker, 14 rue Maria Helena Vieira da Silva, CS 61431, Paris 75014, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Letscher
authors.affiliation: Institut Necker Enfants Malades, Immunology, Infectiology and Haematology Department, Inserm U1151, CNRS UMR 8253, 14 rue Maria Helena Vieira da Silva, CS 61431, Paris 75014, France.|Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine Site Necker, 14 rue Maria Helena Vieira da Silva, CS 61431, Paris 75014, France.
authors.forename: Ruddy
authors.initials: R
authors.lastname: Montandon
authors.affiliation: Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine Site Necker, 14 rue Maria Helena Vieira da Silva, CS 61431, Paris 75014, France.|Structure Fédérative de Recherche Necker, INSERM US 24, CNRS UMS 3633, Paris 75014, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Mégret
authors.affiliation: Department of Biochemistry, University of Lausanne, Epalinges 1066, Switzerland.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Siegert
authors.affiliation: Institut Necker Enfants Malades, Immunology, Infectiology and Haematology Department, Inserm U1151, CNRS UMR 8253, 14 rue Maria Helena Vieira da Silva, CS 61431, Paris 75014, France.|Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine Site Necker, 14 rue Maria Helena Vieira da Silva, CS 61431, Paris 75014, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Ezine
authors.affiliation: Department of Medicine, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland.
authors.forename: Padraic G
authors.initials: PG
authors.lastname: Fallon
authors.affiliation: Department of Biochemistry, University of Lausanne, Epalinges 1066, Switzerland.
authors.forename: Sanjiv A
authors.initials: SA
authors.lastname: Luther
authors.affiliation: Institut Necker Enfants Malades, Immunology, Infectiology and Haematology Department, Inserm U1151, CNRS UMR 8253, 14 rue Maria Helena Vieira da Silva, CS 61431, Paris 75014, France.|Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine Site Necker, 14 rue Maria Helena Vieira da Silva, CS 61431, Paris 75014, France.|Assistance Publique-Hopitaux de Paris (AP-HP), Hopital Necker Enfants Malades, Paris 75015, France.|Deutsches Rheuma-Forschungszentrum, a Leibniz Institute, Chariteplatz 1, Berlin 10117, Germany.
authors.forename: Simon
authors.initials: S
authors.lastname: Fillatreau
authors.affiliation: Institut Necker Enfants Malades, Immunology, Infectiology and Haematology Department, Inserm U1151, CNRS UMR 8253, 14 rue Maria Helena Vieira da Silva, CS 61431, Paris 75014, France.|Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine Site Necker, 14 rue Maria Helena Vieira da Silva, CS 61431, Paris 75014, France.
authors.forename: Flora
authors.identifier: 0000-0002-2338-6802
authors.initials: F
authors.lastname: Zavala
mesh_terms: D000818:Animals; D060151:B-Lymphocytes, Regulatory / Q000166:cytology / Q000502:physiology*; D016026:Bone Marrow Transplantation; D002454:Cell Differentiation; D002465:Cell Movement; D054415:Chemokine CCL19 / Q000502:physiology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000628:therapy*; D005260:Female; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D008198:Lymph Nodes / Q000502:physiology; D008810:Mice, Inbred C57BL; D009838:Oligodeoxyribonucleotides; D054448:Precursor Cells, B-Lymphoid / Q000502:physiology / Q000637:transplantation*
chemical_list: C523579:CPG 10101; C515461:Ccl19 protein, mouse; D054415:Chemokine CCL19; C556062:IL10 protein, mouse; D009838:Oligodeoxyribonucleotides; D016753:Interleukin-10; D007371:Interferon-gamma