PMID- 23958952
OWN - NLM
STAT- MEDLINE
DCOM- 20131118
LR  - 20211203
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 122
IP  - 14
DP  - 2013 Oct 3
TI  - Requirement for Rictor in homeostasis and function of mature B lymphoid cells.
PG  - 2369-79
LID - 10.1182/blood-2013-01-477505 [doi]
AB  - 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 kappaB induction 
      after B-cell receptor stimulation, and B-cell activating factor-induced nuclear 
      factor kappaB2/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.
FAU - Lee, Keunwook
AU  - Lee K
AD  - Departments of Pathology and Microbiology & Pathology, Vanderbilt University 
      School of Medicine, Nashville, TN;
FAU - Heffington, Lindsey
AU  - Heffington L
FAU - Jellusova, Julia
AU  - Jellusova J
FAU - Nam, Ki Taek
AU  - Nam KT
FAU - Raybuck, Ariel
AU  - Raybuck A
FAU - Cho, Sung Hoon
AU  - Cho SH
FAU - Thomas, James W
AU  - Thomas JW
FAU - Rickert, Robert C
AU  - Rickert RC
FAU - Boothby, Mark
AU  - Boothby M
LA  - eng
GR  - AI041649/AI/NIAID NIH HHS/United States
GR  - HL106812/HL/NHLBI NIH HHS/United States
GR  - R01 AI051448/AI/NIAID NIH HHS/United States
GR  - R01 AI041649/AI/NIAID NIH HHS/United States
GR  - R01 HL106812/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20130819
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Carrier Proteins)
RN  - 0 (Rapamycin-Insensitive Companion of mTOR Protein)
RN  - 0 (rictor protein, mouse)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Adoptive Transfer
MH  - Animals
MH  - B-Lymphocytes/*cytology/*immunology
MH  - Blotting, Western
MH  - Carrier Proteins/genetics/*immunology/metabolism
MH  - Cell Differentiation/*immunology
MH  - Cell Proliferation
MH  - Cell Survival/immunology
MH  - Electrophoretic Mobility Shift Assay
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Flow Cytometry
MH  - Homeostasis/*immunology
MH  - Immunohistochemistry
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Rapamycin-Insensitive Companion of mTOR Protein
MH  - Signal Transduction/immunology
MH  - TOR Serine-Threonine Kinases/genetics/immunology/metabolism
PMC - PMC3790507
EDAT- 2013/08/21 06:00
MHDA- 2013/11/19 06:00
PMCR- 2014/10/03
CRDT- 2013/08/21 06:00
PHST- 2013/08/21 06:00 [entrez]
PHST- 2013/08/21 06:00 [pubmed]
PHST- 2013/11/19 06:00 [medline]
PHST- 2014/10/03 00:00 [pmc-release]
AID - S0006-4971(20)49952-5 [pii]
AID - 2013/477505 [pii]
AID - 10.1182/blood-2013-01-477505 [doi]
PST - ppublish
SO  - Blood. 2013 Oct 3;122(14):2369-79. doi: 10.1182/blood-2013-01-477505. Epub 2013 
      Aug 19.