title: MZ B cells migrate in a T-bet dependent manner and might contribute to the remission of collagen-induced arthritis by the secretion of IL-10.
abstract: In mice, marginal zone (MZ) B cells are found principally in the MZ of the spleen and characterized as CD23-negative cells, primarily express polyreactive BCRs, high levels of complement receptor-2 and TLRs. Collagen-induced arthritis (CIA) is a commonly used animal model of human rheumatoid arthritis, considered as a Th1-mediated disease. Although the importance of MZ B cells in the initiation of CIA is well established, their role in remission is unexplored. Besides, playing a central role in Th1 cell development, T-box transcription factor (T-bet) has important functions in B cells. T-bet is regulated by IFN-γ and through the BCR and TLR9, the signals that have an impact on regulatory IL-10 production. In this work, we aimed to analyze the contribution of T-bet to the function of IL-10-positive MZ B cells. We demonstrate that during the remission phase of CIA, MZ B cells express an elevated level of T-bet and confirm the existence of IL-10/T-bet coexpressing cells. Moreover, we show that T-bet-expressing MZ B cells migrate toward CXCR3 ligand and secrete IL-10 by inflammatory stimuli. Our data suggest that T-bet might contribute to the remission of CIA by facilitating the regulatory potential of IL-10-positive MZ B cells.
authors.affiliation: Department of Immunology, Eötvös Loránd University, Budapest, Hungary.
authors.forename: Krisztina
authors.initials: K
authors.lastname: Huber
authors.affiliation: Department of Immunology, Eötvös Loránd University, Budapest, Hungary.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Sármay
authors.affiliation: Department of Immunology, Eötvös Loránd University, Budapest, Hungary. dkovesdi@ttk.elte.hu.
authors.forename: Dorottya
authors.initials: D
authors.lastname: Kövesdi
mesh_terms: D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D001169:Arthritis, Experimental / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D002478:Cells, Cultured; D002633:Chemotaxis / Q000235:genetics / Q000276:immunology*; D005260:Female; D015870:Gene Expression; D007371:Interferon-gamma / Q000494:pharmacology; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D009838:Oligodeoxyribonucleotides / Q000276:immunology; D054367:Receptors, CXCR3 / Q000378:metabolism; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism*; D000098815:T-bet Transcription Factor
chemical_list: D000888:Antibodies, Anti-Idiotypic; D009838:Oligodeoxyribonucleotides; D054367:Receptors, CXCR3; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; C044203:anti-IgM; D016753:Interleukin-10; D007371:Interferon-gamma
keywords: CXCR3; IL-10; Marginal zone B cells; Migration; T-bet