title: Human T cells induce their own regulation through activation of B cells.
abstract: Regulatory functions for B lymphocytes have been reported in murine models of autoimmune diseases in which B-cell deficient mice were shown to exhibit exacerbated disease. The B cells responsible for the immune regulations were identified as a subpopulation of interleukin 10-secreting cells. However, the mechanism of induction and the characteristics of regulatory B cells in humans have been hardly studied. This study reports that regulation of T cell responses can be induced by B cells following CD40-dependent cognate interaction. T cell proliferation and cytokine production were differentially regulated. Thus, CD40-induced regulatory B cells partially inhibited T cell proliferation following CD40 interaction without requirement of soluble factor. In contrast, modulation of Th1 differentiation resulted from CD80- and CD86-dependent interactions and from IL-10 production. The suppressive effects were mediated by CD19(high)IgD+CD38(high)CD24(high)CD5(high) B cells and appeared to be indirect, through the induction of regulatory T cells as indicated by the appearance of Foxp3+CD4+CD25+T cells. These data suggest that activation signals from T cells initiate regulatory properties in B cells that modulate T cell responses involving regulatory T cells. Finally, studies in autoimmune patients revealed that regulation of T cell proliferation was defective in systemic lupus erythematosus but efficient in other diseases. Restoration of efficient B-cell regulatory activity could provide innovative B-cell based treatment of autoimmune diseases.
authors.affiliation: EA 2216 "Immunology and Pathology" and IFR 148 ScInBioS at the European University of Brittany and the University of Brest, Brest, France. sebastien200109@gmail.com
authors.forename: Sébastien
authors.initials: S
authors.lastname: Lemoine
authors.forename: Ahsen
authors.initials: A
authors.lastname: Morva
authors.forename: Pierre
authors.initials: P
authors.lastname: Youinou
authors.forename: Christophe
authors.initials: C
authors.lastname: Jamin
mesh_terms: D015703:Antigens, CD / Q000502:physiology; D001402:B-Lymphocytes / Q000276:immunology*; D018122:B7-1 Antigen / Q000502:physiology; D019013:CD40 Antigens / Q000502:physiology; D023201:CD40 Ligand / Q000502:physiology; D002478:Cells, Cultured; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D008213:Lymphocyte Activation; D013601:T-Lymphocytes / Q000502:physiology*; D050378:T-Lymphocytes, Regulatory / Q000502:physiology; D060225:Tetraspanin 28
chemical_list: D015703:Antigens, CD; D018122:B7-1 Antigen; D019013:CD40 Antigens; C554798:CD81 protein, human; C554799:Cd81 protein, mouse; D060225:Tetraspanin 28; D016753:Interleukin-10; D023201:CD40 Ligand