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.
This work was supported by National Institutes of Health Grants T32AI055428, T32CA009171, R01AI113047, and R01AI108686 and by Department of Defense Grant PR130769. R.S. and W.J.L. were supported by the Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health. B.B. was supported by German Research Foundation Fellowship BE5496/1-1.
The transcriptional profiling data presented in this article have been submitted to the Gene Expression Omnibus (http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE77145) under accession number GSE77145.
The online version of this article contains supplemental material.
Abbreviations used in this article:
- memory B
- germinal center
- A/Puerto Rico/8/1934
- T follicular helper
- Violet Cell Trace
- wild type.
- Received March 29, 2016.
- Accepted June 20, 2016.
- Copyright © 2016 by The American Association of Immunologists, Inc.