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Cell Rep . 2020 Oct 6;

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

Theophilos Tzaridis, Katrin S Reiners, Johannes Weller, Daniel Bachurski, Niklas Schäfer, Christina Schaub, Michael Hallek, Björn Scheffler, Martin Glas, Ulrich Herrlinger, Stefan Wild, Christoph Coch, Gunther Hartmann, Stephanie Fischinger, Sepideh Dolatshahi, Madeleine F Jennewein, Supachai Rerks-Ngarm, Punnee Pitisuttithum, Sorachai Nitayaphan, Nelson L Michael, Sandhya Vasan, Margaret E Ackerman, Hendrik Streeck, Galit Alter, Lianmin Chen, Inge C L van den Munckhof, Kiki Schraa, Rob Ter Horst, Martijn Koehorst, Martijn van Faassen, Claude van der Ley, Marwah Doestzada, Daria V Zhernakova, Alexander Kurilshikov, Vincent W Bloks, Albert K Groen, Human Functional Genomics Project, Niels P Riksen, Joost H W Rutten, Leo A B Joosten, Cisca Wijmenga, Alexandra Zhernakova, Mihai G Netea, Jingyuan Fu, Folkert Kuipers, Dominik Alterauge, Johannes W Bagnoli, Frank Dahlström, Barry M Bradford, Neil A Mabbott, Thorsten Buch, Wolfgang Enard, Dirk Baumjohann

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.

PMID: 33027650