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

• Published in: European journal of immunology 2016-09, Vol.46 (9), p.2239-2246
• Main Authors: Huber, Krisztina, Sármay, Gabriella, Kövesdi, Dorottya
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Anti-Idiotypic - immunology; Arthritis; Arthritis, Experimental - genetics; Arthritis, Experimental - immunology; Arthritis, Experimental - metabolism; B-Lymphocytes - drug effects; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; CD23 antigen; Cell migration; Cells, Cultured; Chemotaxis - genetics; Chemotaxis - immunology; Collagen; CXCR3; CXCR3 protein; Female; Gene Expression; IL‐10; Inflammation; Interferon-gamma - pharmacology; Interleukin 10; Interleukin-10 - genetics; Interleukin-10 - secretion; Lymphocyte Activation - immunology; Lymphocyte receptors; Lymphocytes B; Lymphocytes T; Marginal zone B cells; Mice; Migration; Oligodeoxyribonucleotides - immunology; Receptors, CXCR3 - metabolism; Remission; Rheumatoid arthritis; Spleen; T-Box Domain Proteins - genetics; T-Box Domain Proteins - metabolism; TLR9 protein; Toll-like receptors; T‐bet
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.201546248

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. MZ B cells express an elevated level of T‐bet in the remission phase of CIA. We confirmed the existence of a T‐bet+IL‐10+ subpopulation of MZ B cells, showed that T‐bet+ MZ B cells migrated toward ligand interacting with T‐bet regulated CXCR3 and secreted IL‐10 in response to inflammatory stimuli. .