The Kinase Complex mTOR Complex 2 Promotes the Follicular Migration and Functional Maturation of Differentiated Follicular Helper CD4(+) T Cells During Viral Infection

Follicular helper CD4(+) T (T(FH)) cells are critical for optimal B-cell-mediated humoral immunity by initiating, fueling, and sustaining germinal center reactions. The differentiation of T(FH) cells relies on multiple intrinsic and extrinsic factors; however, the details by which these factors are integrated to coordinate T(FH) differentiation are largely unknown. In this study, using a mouse model of acute lymphocytic choriomeningitis virus (LCMV) viral infection, we demonstrate that mTOR complex 2 (mTORC2) kinase integrates TCR signaling and ICOS-mediated co-stimulation to promote late differentiation and functional maturation of virus-specific T(FH) cells. Specifically, mTORC2 functions to maintain T(FH) lineage specifications, including phenotypes, migratory characteristics, and functional properties. Thus, our results highlight the importance of mTORC2 in guarding T(FH) phenotypic and functional maturation.