Requirement for Rictor in homeostasis & function of mature B lymphoid cells

Keunwook Lee, Lindsey Heffington, Julia Jellusova, Ki Taek Nam, Ariel Raybuck, Sung Hoon Cho, James W. Thomas, Robert C. Rickert, Mark Boothby

Research output: Contribution to journalArticle

48 Citations (Scopus)

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 kB induction after B-cell receptor stimulation, and B-cell activating factor-induced nuclear factor kB2/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. (Blood. 2013;122(14):2369-2379).

Original languageEnglish
Pages (from-to)2369-2379
Number of pages11
JournalBlood
Volume122
Issue number14
DOIs
Publication statusPublished - 2013

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Lee, K., Heffington, L., Jellusova, J., Nam, K. T., Raybuck, A., Cho, S. H., Thomas, J. W., Rickert, R. C., & Boothby, M. (2013). Requirement for Rictor in homeostasis & function of mature B lymphoid cells. Blood, 122(14), 2369-2379. https://doi.org/10.1182/blood-2013-01-477505