Cutting Edge: IL-4, IL-21, and IFN-γ Interact To Govern T-bet and CD11c Expression in TLR-Activated B Cells

作者：Martin S. Naradikian, Arpita Myles, Daniel P. Beiting, Kenneth J Roberts, Lucas Dawson, Ramin S. Herati, Bertram Bengsch, Susanne L. Linderman, Erietta Stelekati, Rosanne Spolski, E. John Wherry, Christopher A. Hunter, Scott E. Hensley, Warren J. Leonard, Michael P. Cancro · 发表于：The Journal of Immunology · 年份：2016 · DOI：10.4049/jimmunol.1600522 · 被引用次数：242 · 研究领域：T-cell and B-cell Immunology、Immune Cell Function and Interaction、Immunotherapy and Immune Responses

T-bet and CD11c expression in B cells is linked with IgG2c isotype switching, virus-specific immune responses, and humoral autoimmunity. However, the activation requisites and regulatory cues governing T-bet and CD11c expression in B cells remain poorly defined. In this article, we reveal a relationship among TLR engagement, IL-4, IL-21, and IFN-γ that regulates T-bet expression in B cells. We find that IL-21 or IFN-γ directly promote T-bet expression in the context of TLR engagement. Further, IL-4 antagonizes T-bet induction. Finally, IL-21, but not IFN-γ, promotes CD11c expression independent of T-bet. Using influenza virus and Heligmosomoides polygyrus infections, we show that these interactions function in vivo to determine whether T-bet(+) and CD11c(+) B cells are formed. These findings suggest that T-bet(+) B cells seen in health and disease share the common initiating features of TLR-driven activation within this circumscribed cytokine milieu.