Requirement for Rictor in homeostasis and function of mature B lymphoid cells.

Lee K, Heffington L, Jellusova J, Nam KT, Raybuck A, Cho SH, Thomas JW, Rickert RC, Boothby M
Blood. 2013 122 (14): 2369-79

PMID: 23958952 · PMCID: PMC3790507 · DOI:10.1182/blood-2013-01-477505

The mammalian target of rapamycin (mTOR), an essential serine/threonine kinase, functions in biochemically distinct multiprotein complexes, but little is known about roles of the complexes in B cells. The acutely rapamycin-sensitive mTOR complex 1 (mTORC1) is defined by a core subunit Raptor, whereas mTORC2 lacks Raptor and, instead, has Rictor and SIN1 as distinct essential components. We now show that homeostasis and function of B cells require Rictor. Conditional deletion of Rictor before lymphoid specification impaired generation of mature follicular, marginal zone, and B1a B lymphocytes. Induced inactivation in adult mice caused cell-autonomous defects in B lymphoid homeostasis and antibody responses in vivo, along with affecting plasma cells in bone marrow. Survival of B lymphocytes depended on Rictor, which was vital for normal induction of prosurvival genes, suppression of proapoptotic genes, nuclear factor κB induction after B-cell receptor stimulation, and B-cell activating factor-induced nuclear factor κB2/p52 generation. Collectively, the findings provide evidence that mTOR signaling affects survival and proliferation of mature B lymphocytes, and establish Rictor as an important signal relay in B-cell homeostasis, fate, and functions.

MeSH Terms (18)

Adoptive Transfer Animals B-Lymphocytes Blotting, Western Carrier Proteins Cell Differentiation Cell Proliferation Cell Survival Electrophoretic Mobility Shift Assay Enzyme-Linked Immunosorbent Assay Flow Cytometry Homeostasis Immunohistochemistry Mice Mice, Inbred C57BL Rapamycin-Insensitive Companion of mTOR Protein Signal Transduction TOR Serine-Threonine Kinases

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