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

ABSTRACT: 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-? that regulates T-bet expression in B cells. We find that IL-21 or IFN-? directly promote T-bet expression in the context of TLR engagement. Further, IL-4 antagonizes T-bet induction. Finally, IL-21, but not IFN-?, 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.

SUBMITTER: Naradikian MS 

PROVIDER: S-EPMC4975960 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature