| Title: |
Context-Dependent Role for T-bet in T Follicular Helper Differentiation and Germinal Center Function following Viral Infection |
| Authors: |
Sheikh, AA; Cooper, L; Feng, M; Souza-Fonseca-Guimaraes, F; Lafouresse, F; Duckworth, BC; Huntington, ND; Moon, JJ; Pellegrini, M; Nutt, SL; Belz, GT; Good-Jacobson, KL; Groom, JR |
| Publisher Information: |
CELL PRESS |
| Publication Year: |
2019 |
| Collection: |
The University of Melbourne: Digital Repository |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| ISSN: |
2211-1247 |
| Relation: |
https://hdl.handle.net/11343/246486 |
| Availability: |
https://hdl.handle.net/11343/246486 |
| Rights: |
https://creativecommons.org/licenses/by-nc-nd/4.0 ; CC BY-NC-ND |
| Accession Number: |
edsbas.983879B4 |
| Database: |
BASE |