Critical roles of mTOR Complex 1 and 2 for T follicular helper cell differentiation and germinal center responses
- Duke University Medical Center, United States
- Wenzhou Medical University, China
- University of Iowa, United States
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.
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Author details
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.
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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Critical roles of mTOR Complex 1 and 2 for T follicular helper cell differentiation and germinal center responses
eLife 5:e17936.
https://doi.org/10.7554/eLife.17936
