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

eLife | 2016

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.

Pubmed ID: 27690224 RIS Download

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Associated grants

  • Agency: NIAID NIH HHS, United States
    Id: R21 AI119160
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI112579
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI101206
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI079088
  • Agency: NIAID NIH HHS, United States
    Id: R21 AI115149

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