Context-dependent role for T-bet in T follicular helper differentiation and germinal center function following viral infection
- Author(s)
- 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;
- Details
- Publication Year 2019-08-13,Volume 28,Issue #7,Page 1758-1772 e4
- Journal Title
- Cell Reports
- Publication Type
- Journal Article
- 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.
- Publisher
- Elsevier
- Research Division(s)
- Immunology; Infectious Diseases And Immune Defence
- PubMed ID
- 31412245
- Publisher's Version
- https://doi.org/10.1016/j.celrep.2019.07.034
- Open Access at Publisher's Site
https://doi.org/10.1016/j.celrep.2019.07.034- NHMRC Grants
- NHMRC/1137989, NHMRC/1057707, NHMRC/1108066, NHMRC/1006592, NHMRC/1045549, NHMRC/1065626, NHMRC/1108066,
- ARC Grants
- ARC/FT130100708,
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2019-08-21 11:19:31
Last Modified: 2019-08-21 11:35:16