Continued Bcl6 Expression Prevents the Transdifferentiation of Established Tfh Cells into Th1 Cells during Acute Viral Infection
Dominik Alterauge,
Johannes W. Bagnoli,
Frank Dahlström,
Barry M. Bradford,
Neil A. Mabbott,
Thorsten Buch,
Wolfgang Enard,
Dirk Baumjohann
Affiliations
Dominik Alterauge
Institute for Immunology, Biomedical Center, Faculty of Medicine, LMU Munich, Grosshaderner Str. 9, 82152 Planegg-Martinsried, Germany
Johannes W. Bagnoli
Anthropology & Human Genomics, Department of Biology II, LMU Munich, Grosshaderner Str. 2, 82152 Planegg-Martinsried, Germany
Frank Dahlström
Institute for Immunology, Biomedical Center, Faculty of Medicine, LMU Munich, Grosshaderner Str. 9, 82152 Planegg-Martinsried, Germany
Barry M. Bradford
The Roslin Institute and the Royal (Dick) School of Veterinary Sciences, University of Edinburgh, Easter Bush, Midlothian EH25 9RG, UK
Neil A. Mabbott
The Roslin Institute and the Royal (Dick) School of Veterinary Sciences, University of Edinburgh, Easter Bush, Midlothian EH25 9RG, UK
Thorsten Buch
Institute of Laboratory Animal Science, University of Zurich, Wagistr. 12, 8952 Schlieren, Switzerland
Wolfgang Enard
Anthropology & Human Genomics, Department of Biology II, LMU Munich, Grosshaderner Str. 2, 82152 Planegg-Martinsried, Germany
Dirk Baumjohann
Institute for Immunology, Biomedical Center, Faculty of Medicine, LMU Munich, Grosshaderner Str. 9, 82152 Planegg-Martinsried, Germany; Medical Clinic III for Oncology, Hematology, Immuno-Oncology, and Rheumatology, University Hospital Bonn, University of Bonn, Venusberg-Campus 1, 53127 Bonn, Germany; Corresponding author
Summary: 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.
