SurveyControl of B lymphocyte development and functions by the mTOR signaling pathways

- The mTOR serine/threonine kinase forms two compositionally and functionally distinct complexes called mTORC1 and mTORC2.
- mTORC1 initiates protein, DNA, and lipid synthesis in response to adequate nutrient availability.
- mTORC2 stimulates cell survival and cytoskeletal reorganization in response to growth factors.
- mTORC1 is modulated by AMPK and the Folliculin/Fnip1/Fnip2 complex.
- mTORC1, mTORC2, Folliculin, and Fnip1 are important for normal murine B cell development and functions.

Mechanistic target of rapamycin (mTOR) is a serine/threonine kinase originally discovered as the molecular target of the immunosuppressant rapamycin. mTOR forms two compositionally and functionally distinct complexes, mTORC1 and mTORC2, which are crucial for coordinating nutrient, energy, oxygen, and growth factor availability with cellular growth, proliferation, and survival. Recent studies have identified critical, non-redundant roles for mTORC1 and mTORC2 in controlling B cell development, differentiation, and functions, and have highlighted emerging roles of the Folliculin-Fnip protein complex in regulating mTOR and B cell development. In this review, we summarize the basic mechanisms of mTOR signaling; describe what is known about the roles of mTORC1, mTORC2, and the Folliculin/Fnip1 pathway in B cell development and functions; and briefly outline current clinical approaches for targeting mTOR in B cell neoplasms. We conclude by highlighting a few salient questions and future perspectives regarding mTOR in B lineage cells.