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. 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.
Duke Scholars
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Related Subject Headings
- T-Lymphocytes, Helper-Inducer
- Mice
- Mechanistic Target of Rapamycin Complex 2
- Mechanistic Target of Rapamycin Complex 1
- Germinal Center
- Cell Differentiation
- Animals
- 42 Health sciences
- 32 Biomedical and clinical sciences
- 31 Biological sciences
Citation
Published In
DOI
EISSN
Publication Date
Volume
Location
Related Subject Headings
- T-Lymphocytes, Helper-Inducer
- Mice
- Mechanistic Target of Rapamycin Complex 2
- Mechanistic Target of Rapamycin Complex 1
- Germinal Center
- Cell Differentiation
- Animals
- 42 Health sciences
- 32 Biomedical and clinical sciences
- 31 Biological sciences