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.

Keywords: CXCR3; IL-10; Marginal zone B cells; Migration; T-bet.