Context-Dependent Role for T-bet in T Follicular Helper Differentiation and Germinal Center Function following Viral Infection

Publication date: 13 August 2019Source: Cell Reports, Volume 28, Issue 7Author(s): Amania A. Sheikh, Lucy Cooper, Meiqi Feng, Fernando Souza-Fonseca-Guimaraes, Fanny Lafouresse, Brigette C. Duckworth, Nicholas D. Huntington, James J. Moon, Marc Pellegrini, Stephen L. Nutt, Gabrielle T. Belz, Kim L. Good-Jacobson, Joanna R. GroomSummaryFollowing infection, inflammatory cues upregulate core transcriptional programs to establish pathogen-specific protection. In viral infections, T follicular helper (TFH) cells express the prototypical T helper 1 transcription factor T-bet. Several studies have demonstrated essential but conflicting roles for T-bet in TFH biology. Understanding the basis of this controversy is crucial, as modulation of T-bet expression instructs TFH differentiation and ultimately protective antibody responses. Comparing influenza and LCMV viral infections, we demonstrate that the role of T-bet is contingent on the environmental setting of TFH differentiation, IL-2 signaling, and T cell competition. Furthermore, we demonstrate that T-bet expression by either TFH or GC B cells independently drives antibody isotype class switching. Specifically, T cell-specific loss of T-bet promotes IgG1, whereas B cell-specific loss of T-bet inhibits IgG2a/c switching. Combined, this work highlights that the context-dependent induction of T-bet instructs the development of protective, neutralizing antibodies following viral infection or vaccination.Graphical Abstract
Source: Cell Reports - Category: Cytology Source Type: research

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