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 journalArticlepeer-review

50 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

Bibliographical note

Funding Information:
This study was supported by National Institutes of Health, National Heart, Lung, and Blood Institute (grant HL106812 to M.B.), and National Institute of Allergy and Infectious Diseases (grant AI041649 to R.R.).

Funding Information:
We thank Vanderbilt cores and institutional Cancer Center Support Grant and Diabetes Center grants.

Publisher Copyright:
©2013 by The American Society of Hematology.

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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