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Ciucci T, Vacchio MS, Chen T, et al. Dependence on Bcl6 and Blimp1 drive distinct differentiation of murine memory and follicular helper CD4+ T cells. J Exp Med. 2021;219(1)doi: 10.1084/jem.20202343.
Ciucci, T., Vacchio, M. S., Chen, T., Nie, J., Chopp, L. B., McGavern, D. B., Kelly, M. C., & Bosselut, R. (2022). Dependence on Bcl6 and Blimp1 drive distinct differentiation of murine memory and follicular helper CD4+ T cells. The Journal of experimental medicine, 219(1), . https://doi.org/10.1084/jem.20202343
Ciucci, Thomas, et al. "Dependence on Bcl6 and Blimp1 drive distinct differentiation of murine memory and follicular helper CD4+ T cells." The Journal of experimental medicine vol. 219,1 (2022). doi: https://doi.org/10.1084/jem.20202343
Ciucci T, Vacchio MS, Chen T, Nie J, Chopp LB, McGavern DB, Kelly MC, Bosselut R. Dependence on Bcl6 and Blimp1 drive distinct differentiation of murine memory and follicular helper CD4+ T cells. J Exp Med. 2022 Jan 03;219(1). doi: 10.1084/jem.20202343. Epub 2021 Nov 18. PMID: 34792530; PMCID: PMC8605495.
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J Exp Med. 2022 Jan 03;219(1). doi: 10.1084/jem.20202343. Epub 2021 Nov 18.

Dependence on Bcl6 and Blimp1 drive distinct differentiation of murine memory and follicular helper CD4+ T cells.

The Journal of experimental medicine

Thomas Ciucci, Melanie S Vacchio, Ting Chen, Jia Nie, Laura B Chopp, Dorian B McGavern, Michael C Kelly, Rémy Bosselut

Affiliations

  1. Laboratory of Immune Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD.
  2. David H. Smith Center for Vaccine Biology and Immunology, Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY.
  3. Immunology Graduate Group, University of Pennsylvania Medical School, Philadelphia, PA.
  4. Viral Immunology and Intravital Imaging Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD.
  5. Single Cell Analysis Facility, Cancer Research Technology Program, Frederick National Laboratory, Bethesda, MD.

PMID: 34792530 PMCID: PMC8605495 DOI: 10.1084/jem.20202343

Abstract

During the immune response, CD4+ T cells differentiate into distinct effector subtypes, including follicular helper T (Tfh) cells that help B cells, and into memory cells. Tfh and memory cells are required for long-term immunity; both depend on the transcription factor Bcl6, raising the question whether they differentiate through similar mechanisms. Here, using single-cell RNA and ATAC sequencing, we show that virus-responding CD4+ T cells lacking both Bcl6 and Blimp1 can differentiate into cells with transcriptomic, chromatin accessibility, and functional attributes of memory cells but not of Tfh cells. Thus, Bcl6 promotes memory cell differentiation primarily through its repression of Blimp1. These findings demonstrate that distinct mechanisms underpin the differentiation of memory and Tfh CD4+ cells and define the Bcl6-Blimp1 axis as a potential target for promoting long-term memory T cell differentiation.

This is a work of the U.S. Government and is not subject to copyright protection in the United States. Foreign copyrights may apply.

Conflict of interest statement

Disclosures: The authors declare no competing interests exist.

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