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

08:00 EDT 13th August 2019 | BioPortfolio

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

Following 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.


Journal Details

This article was published in the following journal.

Name: Cell reports
ISSN: 2211-1247
Pages: 1758-1772.e4


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