PMID- 28557002
OWN - NLM
STAT- MEDLINE
DCOM- 20171002
LR  - 20211204
IS  - 1365-2567 (Electronic)
IS  - 0019-2805 (Print)
IS  - 0019-2805 (Linking)
VI  - 152
IP  - 2
DP  - 2017 Oct
TI  - Mammalian target of rapamycin complex 1 signalling is essential for germinal 
      centre reaction.
PG  - 276-286
LID - 10.1111/imm.12767 [doi]
AB  - The mammalian target of rapamycin (mTOR) is a serine-threonine kinase that has 
      been shown to be essential for the differentiation and function of various immune 
      cells. Earlier in vitro studies showed that mTOR signalling regulates B-cell 
      biology by supporting their activation and proliferation. However, how mTOR 
      signalling temporally regulates in vivo germinal centre B (GCB) cell development 
      and differentiation into short-lived plasma cells, long-lived plasma cells and 
      memory cells is still not well understood. In this study, we used a combined 
      conditional/inducible knock-out system to investigate the temporal regulation of 
      mTOR complex 1 (mTORC1) in the GCB cell response to acute lymphocytic 
      choriomeningitis virus infection by deleting Raptor, a main component of mTORC1, 
      specifically in B cells in pre- and late GC phase. Early Raptor deficiency 
      strongly inhibited GCB cell proliferation and differentiation and plasma cell 
      differentiation. Nevertheless, late GC Raptor deficiency caused only decreases in 
      the size of memory B cells and long-lived plasma cells through poor maintenance 
      of GCB cells, but it did not change their differentiation. Collectively, our data 
      revealed that mTORC1 signalling supports GCB cell responses at both early and 
      late GC phases during viral infection but does not regulate GCB cell 
      differentiation into memory B cells and plasma cells at the late GC stage.
CI  - (c) 2017 John Wiley & Sons Ltd.
FAU - Li, Bingshou
AU  - Li B
AD  - Institute of Immunology, PLA, Third Military Medical University, Chongqing, 
      China.
FAU - Li, Zhirong
AU  - Li Z
AD  - Institute of Immunology, PLA, Third Military Medical University, Chongqing, 
      China.
FAU - Wang, Pengcheng
AU  - Wang P
AD  - Institute of Immunology, PLA, Third Military Medical University, Chongqing, 
      China.
FAU - Huang, Qizhao
AU  - Huang Q
AD  - Institute of Immunology, PLA, Third Military Medical University, Chongqing, 
      China.
FAU - Xu, Lifan
AU  - Xu L
AD  - Institute of Immunology, PLA, Third Military Medical University, Chongqing, 
      China.
FAU - He, Ran
AU  - He R
AD  - Institute of Immunology, PLA, Third Military Medical University, Chongqing, 
      China.
FAU - Ye, Lilin
AU  - Ye L
AD  - Institute of Immunology, PLA, Third Military Medical University, Chongqing, 
      China.
FAU - Bai, Qiang
AU  - Bai Q
AUID- ORCID: 0000-0001-7423-0712
AD  - Institute of Immunology, PLA, Third Military Medical University, Chongqing, 
      China.
LA  - eng
PT  - Journal Article
DEP - 20170710
PL  - England
TA  - Immunology
JT  - Immunology
JID - 0374672
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Multiprotein Complexes)
RN  - 0 (Regulatory-Associated Protein of mTOR)
RN  - 0 (Rptor protein, mouse)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing/deficiency/genetics/immunology/*metabolism
MH  - Animals
MH  - B-Lymphocytes/*enzymology/immunology/transplantation/virology
MH  - Bone Marrow Transplantation
MH  - Cell Differentiation
MH  - Cell Proliferation
MH  - Disease Models, Animal
MH  - Genetic Predisposition to Disease
MH  - Germinal Center/*enzymology/immunology/virology
MH  - Host-Pathogen Interactions
MH  - Immunity, Humoral
MH  - Immunologic Memory
MH  - Lymphocyte Activation
MH  - Lymphocytic Choriomeningitis/*enzymology/genetics/immunology/virology
MH  - Lymphocytic choriomeningitis virus/*immunology/pathogenicity
MH  - Mechanistic Target of Rapamycin Complex 1
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Multiprotein Complexes/deficiency/genetics/immunology/*metabolism
MH  - Phenotype
MH  - Plasma Cells/enzymology/immunology/virology
MH  - Regulatory-Associated Protein of mTOR
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases/deficiency/genetics/immunology/*metabolism
MH  - Time Factors
MH  - Transplantation Chimera
PMC - PMC5588811
OTO - NOTNLM
OT  - B cell
OT  - cell differentiation
OT  - gene regulation
EDAT- 2017/05/31 06:00
MHDA- 2017/10/03 06:00
PMCR- 2018/10/01
CRDT- 2017/05/31 06:00
PHST- 2017/01/11 00:00 [received]
PHST- 2017/05/04 00:00 [revised]
PHST- 2017/05/25 00:00 [accepted]
PHST- 2017/05/31 06:00 [pubmed]
PHST- 2017/10/03 06:00 [medline]
PHST- 2017/05/31 06:00 [entrez]
PHST- 2018/10/01 00:00 [pmc-release]
AID - IMM12767 [pii]
AID - 10.1111/imm.12767 [doi]
PST - ppublish
SO  - Immunology. 2017 Oct;152(2):276-286. doi: 10.1111/imm.12767. Epub 2017 Jul 10.