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.