Context-Dependent Role for T-bet in T Follicular Helper Differentiation and Germinal Center Function following Viral Infection.
Cell Rep
; 28(7): 1758-1772.e4, 2019 08 13.
Article
in En
| MEDLINE
| ID: mdl-31412245
ABSTRACT
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Orthomyxoviridae
/
Cell Differentiation
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T-Lymphocytes, Helper-Inducer
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Germinal Center
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T-Box Domain Proteins
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Lymphocytic choriomeningitis virus
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Antibody Formation
Limits:
Animals
Language:
En
Journal:
Cell Rep
Year:
2019
Document type:
Article
Affiliation country: