title: Characterization and Immunoregulatory Properties of Innate Pro-B-Cell Progenitors.
abstract: Control of T-cell responses can be achieved by several subsets of B cells with immunoregulatory functions, mostly acting by provision of the anti-inflammatory cytokine IL-10 or exhibiting killing properties through Fas ligand (Fas-L) or granzyme B-induced cell death. We herein describe the characterization as well as the cellular and molecular mechanisms mediating the suppressive properties of bone marrow immature innate pro-B cell progenitors that emerge upon transient activation of Toll-like receptor 9. They are licensed by activated T-cell-derived IFN-γ to become suppressive by up-regulating their Fas-L expression and inducing effector CD4(+) T-cell apoptosis. They also up-regulate their own IFN-γ production which dramatically reduces T-cell production of a major pathogenic cytokine, IL-21. A single adoptive transfer of as little as 60,000 of them efficiently prevents the onset of spontaneous type 1 diabetes in recipient nonobese diabetes (NOD) mice, highlighting the remarkable regulatory potency of these so-called CpG-proB cell progenitors compared to regulatory cells of diverse lineages so far described. The CpG-proB cell activity is prolonged in vivo by their differentiation after migration in the pancreas and the spleen into B-cell progeny with high Fas-L expression that can keep up inducing apoptosis of effector T cells in the long term.
authors.affiliation: Institut Necker Enfants Malades, INSERM U1151, CNRS UMR8253, Sorbonne Paris Cité, Université Paris Descartes Site Broussais, 14 rue Maria Helena Vieira da Silva, CS 61431, Paris, Cedex 14, 75993, France. flora.zavala@inserm.fr.
authors.forename: Flora
authors.initials: F
authors.lastname: Zavala
authors.affiliation: Institut Necker Enfants Malades, INSERM U1151, CNRS UMR8253, Sorbonne Paris Cité, Université Paris Descartes Site Broussais, 14 rue Maria Helena Vieira da Silva, CS 61431, Paris, Cedex 14, 75993, France.
authors.forename: Sarantis
authors.initials: S
authors.lastname: Korniotis
authors.affiliation: Welcome Trust Sanger Institute, Genome Campus, Cambridge, Hinxton, CB10 1SA, UK.
authors.forename: Ruddy
authors.initials: R
authors.lastname: Montandon
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology; D002450:Cell Communication / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000378:metabolism; D053222:Fas Ligand Protein / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance; D007113:Immunity, Innate; D056747:Immunomodulation; D008213:Lymphocyte Activation / Q000276:immunology; D054448:Precursor Cells, B-Lymphoid / Q000166:cytology* / Q000502:physiology*; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D051193:Toll-Like Receptors / Q000378:metabolism
chemical_list: D016207:Cytokines; D053222:Fas Ligand Protein; D051193:Toll-Like Receptors
keywords: B-cell progenitors; Cell therapy; Fas-L; IFN-γ; IL-21; Killer B lymphocytes; Regulatory B cells; Tolerance; Toll-like receptors; Type 1 diabetes