Cutting Edge: IL-4, IL-21, and IFN-g Interact to Govern TBET and CD11c Expression in TLR-Activated B Cells

T-Box Expressed in T cells (TBET) 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 TBET and CD11c expression remain poorly defined. In this article, we reveal a relationship among TLR engagement, IL-4, IL-21, and IFN-g that regulates TBET expression in B cells. We find that IL-21 or IFN-g directly promote TBET+ expression in the context of TLR engagement. Further, IL-4 antagonizes TBET induction. Finally, IL-21, but not IFN-g, promotes CD11c expression independent of TBET. Using influenza virus and Heligmosomoides polygyrus infections, we show that these interactions function in vivo to determine whether TBET+ and CD11c+ B cells are formed. These findings suggest that TBET+ B cells seen in health and disease share the common initiating features of TLR-driven activation within this circumscribed cytokine milieu. Splenic B cells from replicate mice, for two different genotypes (WT and Tbx21-/-), were stimulated with either interferon-gamma (IFNG) or interleukin-21 (IL21).