1. Immunology and Inflammation
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Critical roles of mTOR Complex 1 and 2 for T follicular helper cell differentiation and germinal center responses

  1. Jialong Yang
  2. Xingguang Lin
  3. Yun Pan
  4. Jinli Wang
  5. Pengcheng Chen
  6. Hongxiang Huang
  7. Hai-Hui Xue
  8. Jimin Gao
  9. Xiao-Ping Zhong  Is a corresponding author
  1. Duke University Medical Center, United States
  2. Wenzhou Medical University, China
  3. University of Iowa, United States
Research Article
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Cite this article as: eLife 2016;5:e17936 doi: 10.7554/eLife.17936

Abstract

T Follicular helper T (Tfh) cells play critical roles for germinal center responses and effective humoral immunity. We report here that mTOR in CD4 T cells is essential for Tfh differentiation. In Mtorf/f-Cd4Cre mice, both constitutive and inducible Tfh differentiation is severely impaired, leading to defective germinal center B cell formation and antibody production. Moreover, both mTORC1 and mTORC2 contribute to Tfh and GC B cell development but may do so via distinct mechanisms. mTORC1 mainly promotes CD4 T cell proliferation to reach the cell divisions necessary for Tfh differentiation, while Rictor/mTORC2 regulates Tfh differentiation by promoting Akt activation and TCF1 expression without grossly influencing T cell proliferation. Together, our results reveal crucial but distinct roles for mTORC1 and mTORC2 in CD4 T cells during Tfh differentiation and germinal center responses.

Article and author information

Author details

  1. Jialong Yang

    Department of Pediatrics, Duke University Medical Center, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Xingguang Lin

    Department of Pediatrics, Duke University Medical Center, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Yun Pan

    Department of Pediatrics, Duke University Medical Center, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Jinli Wang

    School of Laboratory Medicine, Wenzhou Medical University, Wenzhou, China
    Competing interests
    The authors declare that no competing interests exist.
  5. Pengcheng Chen

    School of Laboratory Medicine, Wenzhou Medical University, Wenzhou, China
    Competing interests
    The authors declare that no competing interests exist.
  6. Hongxiang Huang

    Department of Pediatrics, Duke University Medical Center, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Hai-Hui Xue

    Department of Microbiology, University of Iowa, Iowa, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Jimin Gao

    School of Laboratory Medicine, Wenzhou Medical University, Wenzhou, China
    Competing interests
    The authors declare that no competing interests exist.
  9. Xiao-Ping Zhong

    Department of Pediatrics, Duke University Medical Center, Durham, United States
    For correspondence
    xiaoping.zhong@duke.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4619-8783

Funding

National Institutes of Health (R01AI079088)

  • Xiao-Ping Zhong

National Institutes of Health (R01AI101206)

  • Xiao-Ping Zhong

National Institutes of Health (R01AI112579)

  • Hai-Hui Xue

National Institutes of Health (R01AI115149)

  • Hai-Hui Xue

National Institutes of Health (R01AI119160)

  • Hai-Hui Xue

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols A051-16-03 and A095-13-04) of Duke University.

Reviewing Editor

  1. Satyajit Rath, National Institute of Immunology, India

Publication history

  1. Received: May 18, 2016
  2. Accepted: September 28, 2016
  3. Accepted Manuscript published: September 30, 2016 (version 1)
  4. Version of Record published: October 13, 2016 (version 2)

Copyright

© 2016, Yang et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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