| First Author | Sheikh AA | Year | 2019 |
| Journal | Cell Rep | Volume | 28 |
| Issue | 7 | Pages | 1758-1772.e4 |
| PubMed ID | 31412245 | Mgi Jnum | J:288870 |
| Mgi Id | MGI:6431874 | Doi | 10.1016/j.celrep.2019.07.034 |
| Citation | Sheikh AA, et al. (2019) 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 |
| abstractText | 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. |
