Critical roles of mTOR Complex 1 and 2 for T follicular helper cell differentiation and germinal center responses.
T follicular helper (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. InMtorf/f-Cd4Cremice, 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.
Department of Pediatrics, Division of Allergy and Immunology, Duke University Medical Center, Durham, United States.
Jialong
J
Yang
Department of Pediatrics, Division of Allergy and Immunology, Duke University Medical Center, Durham, United States.
Xingguang
X
Lin
Department of Pediatrics, Division of Allergy and Immunology, Duke University Medical Center, Durham, United States.
Yun
Y
Pan
School of Laboratory Medicine, Wenzhou Medical University, Wenzhou, China.
Jinli
J
Wang
School of Laboratory Medicine, Wenzhou Medical University, Wenzhou, China.
Pengcheng
P
Chen
Department of Pediatrics, Division of Allergy and Immunology, Duke University Medical Center, Durham, United States.
Hongxiang
H
Huang
Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa, United States.
Hai-Hui
HH
Xue
School of Laboratory Medicine, Wenzhou Medical University, Wenzhou, China.
Jimin
J
Gao
Department of Pediatrics, Division of Allergy and Immunology, Duke University Medical Center, Durham, United States.|Department of Immunology, Duke University Medical Center, Durham, United States.|Hematologic Malignancies and Cellular Therapies Program, Duke Cancer Institute, Duke University Medical Center, Durham, United States.
Xiao-Ping
0000-0002-4619-8783
XP
Zhong
D000818:Animals; D002454:Cell Differentiation; D018858:Germinal Center / Q000166:cytology*; D000076222:Mechanistic Target of Rapamycin Complex 1 / Q000378:metabolism*; D000076225:Mechanistic Target of Rapamycin Complex 2 / Q000378:metabolism*; D051379:Mice; D006377:T-Lymphocytes, Helper-Inducer / Q000502:physiology*
D000076222:Mechanistic Target of Rapamycin Complex 1; D000076225:Mechanistic Target of Rapamycin Complex 2
T Follicular Helper Cell; germinal center B cell; immunology; lymphocyte subsets; mTOR; mouse; signal transduction
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