PMID- 34964999
OWN - NLM
STAT- MEDLINE
DCOM- 20220420
LR  - 20230402
IS  - 1098-2744 (Electronic)
IS  - 0899-1987 (Print)
IS  - 0899-1987 (Linking)
VI  - 61
IP  - 4
DP  - 2022 Apr
TI  - Conditional deletion of mTOR discloses its essential role in early B-cell 
      development.
PG  - 408-416
LID - 10.1002/mc.23386 [doi]
AB  - Mechanistic target of rapamycin (mTOR) is a serine-threonine kinase and central 
      regulator of cell growth, differentiation, and survival. mTOR is commonly 
      hyperactivated in a diverse number of cancers and critical roles for mTOR in 
      regulating immune cell differentiation and function have been demonstrated. 
      However, there is little work investigating the roles of mTOR in early B-cell 
      development. Here we demonstrate that conditional disruption of mTOR in 
      developing mouse B cells results in reduced pre-B-cell proliferation and 
      survival, as well as a developmental block at the pre-B-cell stage, with a 
      corresponding lack of peripheral B cells. Upon immunization with NP-CGG antigen, 
      mice with Mtor conditional disruption in early B cells lost their ability to form 
      germinal centers and produce specific antibodies. In competitive BM repopulation 
      assays, donor BM cells from conditional knock-out mice were completely impaired 
      in their ability to reconstitute B cells. Our data reveal the essential role of 
      mTOR in early pre-B-cell development and survival.
CI  - (c) 2021 Wiley Periodicals LLC. This article has been contributed to by US 
      Government employees and their work is in the public domain in the USA.
FAU - Zhang, Shuling
AU  - Zhang S
AD  - Laboratory of Cancer Biology and Genetics, National Cancer Institute, National 
      Institutes of Health, Bethesda, Maryland, USA.
FAU - Dubois, Wendy
AU  - Dubois W
AD  - Laboratory of Cancer Biology and Genetics, National Cancer Institute, National 
      Institutes of Health, Bethesda, Maryland, USA.
FAU - Feng, Xingmin
AU  - Feng X
AD  - Hematology Branch, National Heart, Lung, and Blood Institute; National Institutes 
      of Health, Bethesda, Maryland, USA.
FAU - Nguyen, Joe T
AU  - Nguyen JT
AD  - Laboratory of Cancer Biology and Genetics, National Cancer Institute, National 
      Institutes of Health, Bethesda, Maryland, USA.
FAU - Young, Neal S
AU  - Young NS
AD  - Hematology Branch, National Heart, Lung, and Blood Institute; National Institutes 
      of Health, Bethesda, Maryland, USA.
FAU - Mock, Beverly A
AU  - Mock BA
AUID- ORCID: 0000-0003-2479-4549
AD  - Laboratory of Cancer Biology and Genetics, National Cancer Institute, National 
      Institutes of Health, Bethesda, Maryland, USA.
LA  - eng
GR  - Z01 BC010008/ImNIH/Intramural NIH HHS/United States
GR  - Z01 HL002315/ImNIH/Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
DEP - 20211229
PL  - United States
TA  - Mol Carcinog
JT  - Molecular carcinogenesis
JID - 8811105
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - B-Lymphocytes/metabolism
MH  - Cell Differentiation
MH  - Lymphocyte Activation
MH  - Mice
MH  - Mice, Knockout
MH  - *Signal Transduction
MH  - *Sirolimus
MH  - TOR Serine-Threonine Kinases/metabolism
PMC - PMC8930614
MID - NIHMS1765658
OTO - NOTNLM
OT  - B-cell development
OT  - Mb1-Cre mice
OT  - antibody production
OT  - competitive BM transplantation
OT  - mTOR
COIS- Conflict of Interest: The authors declare no competing financial interests.
EDAT- 2021/12/30 06:00
MHDA- 2022/04/21 06:00
PMCR- 2023/04/01
CRDT- 2021/12/29 12:39
PHST- 2021/12/06 00:00 [revised]
PHST- 2021/11/07 00:00 [received]
PHST- 2021/12/10 00:00 [accepted]
PHST- 2021/12/30 06:00 [pubmed]
PHST- 2022/04/21 06:00 [medline]
PHST- 2021/12/29 12:39 [entrez]
PHST- 2023/04/01 00:00 [pmc-release]
AID - 10.1002/mc.23386 [doi]
PST - ppublish
SO  - Mol Carcinog. 2022 Apr;61(4):408-416. doi: 10.1002/mc.23386. Epub 2021 Dec 29.