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

Authors
 Keunwook Lee ; Lindsey Heffington ; Mark Boothby ; Robert C. Rickert ; James W. Thomas ; Sung Hoon Cho ; Ariel Raybuck ; Ki Taek Nam ; Julia Jellusova 
Citation
 Blood, Vol.122(14) : 2369~2379, 2013 
Journal Title
 Blood 
ISSN
 0006-4971 
Issue Date
2013
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.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/88881
DOI
10.1182/blood-2013-01-477505
Appears in Collections:
1. 연구논문 > 1. College of Medicine > Dept. of Life Science
Yonsei Authors
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Link
 http://bloodjournal.hematologylibrary.org/cgi/pmidlookup?view=long&pmid=23958952
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