Continued Bcl6 Expression Prevents the Transdifferentiation of Established Tfh Cells into Th1 Cells during Acute Viral Infection

• Published in: Cell reports (Cambridge) Vol. 33; no. 1; p. 108232
• Main Authors: Alterauge, Dominik, Bagnoli, Johannes W., Dahlström, Frank, Bradford, Barry M., Mabbott, Neil A., Buch, Thorsten, Enard, Wolfgang, Baumjohann, Dirk
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 06.10.2020; Elsevier
• Subjects: Bcl6; CXCR5; flexibility; germinal center; LCMV; maintenance; plasticity; T helper cell; Tfh cell; Th1; flexibility; LCMV; Bcl6; CXCR5; plasticity; Tfh cell; germinal center; Th1; maintenance; T helper cell
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2020.108232

T follicular helper (Tfh) cells are crucial for the establishment of germinal centers (GCs) and potent antibody responses. Nevertheless, the T cell-intrinsic factors that are required for the maintenance of already-established Tfh cells and GCs remain largely unknown. Here, we use temporally guided gene ablation in CD4+ T cells to dissect the contributions of the Tfh-associated chemokine receptor CXCR5 and the transcription factor Bcl6. Induced ablation of Cxcr5 has minor effects on the function of established Tfh cells, and Cxcr5-ablated cells still exhibit most of the features of CXCR5+ Tfh cells. In contrast, continued Bcl6 expression is critical to maintain the GC Tfh cell phenotype and also the GC reaction. Importantly, Bcl6 ablation during acute viral infection results in the transdifferentiation of established Tfh into Th1 cells, thus highlighting the plasticity of Tfh cells. These findings have implications for strategies that boost or restrain Tfh cells and GCs in health and disease. [Display omitted] •Induced ablation of Cxcr5 has minor effects on Tfh cell identity and function•Continued Bcl6 expression is critical for the maintenance of established Tfh cells•CD4+ T cell-expressed Bcl6 is important for the maintenance of germinal centers•Induced ablation of Bcl6 converts “ex-Tfh” cells into Th1 cells during LCMV infection Alterauge et al. show that the induced loss of CXCR5 in established T follicular helper (Tfh) cells has minor effects on Tfh cell identity and germinal center (GC) maintenance. In contrast, induced Bcl6 ablation in CD4+ T cells results in GC resolution and transdifferentiation of established Tfh cells into Th1 cells during acute viral infection.