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

Overview

Journal J Immunol

Specialty Allergy & Immunology

Date 2016 Jul 20

PMID 27430719

Citations 126

Authors

Martin S Naradikian

Arpita Myles

Daniel P Beiting

Kenneth J Roberts

Lucas Dawson

Ramin Sedaghat Herati

Bertram Bengsch

Susanne L Linderman

Erietta Stelekati

Rosanne Spolski

E John Wherry

Christopher Hunter

Scott E Hensley

Warren J Leonard

Michael P Cancro

Affiliations

Soon will be listed here.

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-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.

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