Requirement for Rictor in homeostasis and function of mature B lymphoid cells
Keunwook Lee1, Lindsey Heffington, Julia Jellusova
1Departments of Pathology and Microbiology & Pathology, Vanderbilt University School of Medicine, Nashville, TN;
Abstract:
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.
Insights
Rictor is essential for B cell survival and function. This study shows Rictor
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- The mammalian target of rapamycin (mTOR) is a key kinase regulating cell processes.
- mTOR functions in distinct complexes (mTORC1 and mTORC2), but their roles in B cells are unclear.
- mTORC1 contains Raptor; mTORC2 contains Rictor and SIN1.
Purpose of the Study:
- To investigate the role of Rictor in B cell homeostasis and function.
- To determine how Rictor influences B cell survival, proliferation, and antibody responses.
Main Methods:
- Conditional deletion of Rictor in mice at different developmental stages.
- Analysis of B cell populations, antibody production, and gene expression.
- Assessment of signaling pathways, including nuclear factor κB (NF-κB).
Main Results:
- Rictor is required for the generation of mature B cell subsets (follicular, marginal zone, B1a).
- Rictor inactivation in adult mice impairs B cell homeostasis and antibody responses.
- Rictor is crucial for B cell survival by regulating prosurvival and proapoptotic genes.
- Rictor is vital for NF-κB induction following B-cell receptor stimulation and B-cell activating factor (BAFF) signaling.
Conclusions:
- mTOR signaling, specifically via Rictor, is critical for mature B lymphocyte survival and proliferation.
- Rictor acts as a key signal transducer in B cell homeostasis, development, and function.
- These findings highlight Rictor as a potential therapeutic target in B cell-related diseases.
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