Cutting edge: IL-4, IL-21, and IFN-γ interact to govern T-bet and CD11c expression in TLR-activated B cells

MS Naradikian, A Myles, DP Beiting… - The Journal of …, 2016 - journals.aai.org
MS Naradikian, A Myles, DP Beiting, KJ Roberts, L Dawson, RS Herati, B Bengsch…
The Journal of Immunology, 2016journals.aai.org
T-bet and CD11c expression in B cells is linked with IgG 2c 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 …
Abstract
T-bet and CD11c expression in B cells is linked with IgG 2c 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.
journals.aai.org