PMID- 22267219
OWN - NLM
STAT- MEDLINE
DCOM- 20120404
LR  - 20211021
IS  - 1529-2916 (Electronic)
IS  - 1529-2908 (Print)
IS  - 1529-2908 (Linking)
VI  - 13
IP  - 3
DP  - 2012 Jan 22
TI  - A self-reinforcing regulatory network triggered by limiting IL-7 activates 
      pre-BCR signaling and differentiation.
PG  - 300-7
LID - 10.1038/ni.2210 [doi]
AB  - The molecular crosstalk between the interleukin 7 receptor (IL-7R) and the 
      precursor to the B cell antigen receptor (pre-BCR) in B lymphopoiesis has not 
      been elucidated. Here we demonstrate that in pre-B cells, the IL-7R but not the 
      pre-BCR was coupled to phosphatidylinositol-3-OH kinase (PI(3)K) and the kinase 
      Akt; signaling by this pathway inhibited expression of recombination-activating 
      gene 1 (Rag1) and Rag2. Attenuation of IL-7 signaling resulted in upregulation of 
      the transcription factors Foxo1 and Pax5, which coactivated many pre-B cell 
      genes, including Rag1, Rag2 and Blnk. Induction of Blnk (which encodes the 
      signaling adaptor BLNK) enabled pre-BCR signaling via the signaling molecule Syk 
      and promoted immunoglobulin light-chain rearrangement. BLNK expression also 
      antagonized Akt activation, thereby augmenting the accumulation of Foxo1 and 
      Pax5. This self-reinforcing molecular circuit seemed to sense limiting 
      concentrations of IL-7 and functioned to constrain the proliferation of pre-B 
      cells and trigger their differentiation.
FAU - Ochiai, Kyoko
AU  - Ochiai K
AD  - Department of Molecular Genetics and Cell Biology, The University of Chicago, 
      Chicago, Illinois, USA.
FAU - Maienschein-Cline, Mark
AU  - Maienschein-Cline M
FAU - Mandal, Malay
AU  - Mandal M
FAU - Triggs, Joseph R
AU  - Triggs JR
FAU - Bertolino, Eric
AU  - Bertolino E
FAU - Sciammas, Roger
AU  - Sciammas R
FAU - Dinner, Aaron R
AU  - Dinner AR
FAU - Clark, Marcus R
AU  - Clark MR
FAU - Singh, Harinder
AU  - Singh H
LA  - eng
GR  - P50 GM081892/GM/NIGMS NIH HHS/United States
GR  - GM088847/GM/NIGMS NIH HHS/United States
GR  - HHMI/Howard Hughes Medical Institute/United States
GR  - GM081892/GM/NIGMS NIH HHS/United States
GR  - R01 GM088847/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20120122
PL  - United States
TA  - Nat Immunol
JT  - Nature immunology
JID - 100941354
RN  - 0 (Forkhead Box Protein O1)
RN  - 0 (Forkhead Transcription Factors)
RN  - 0 (Foxo1 protein, mouse)
RN  - 0 (Interleukin-7)
RN  - 0 (PAX5 Transcription Factor)
RN  - 0 (Pax5 protein, mouse)
RN  - 0 (Receptors, Antigen, B-Cell)
SB  - IM
MH  - Animals
MH  - B-Lymphocytes/cytology/*immunology
MH  - *Cell Differentiation
MH  - Cells, Cultured
MH  - Forkhead Box Protein O1
MH  - Forkhead Transcription Factors/immunology
MH  - Interleukin-7/*immunology
MH  - Mice
MH  - PAX5 Transcription Factor/immunology
MH  - Receptors, Antigen, B-Cell/*immunology/metabolism
MH  - *Signal Transduction
PMC - PMC4028049
MID - NIHMS491544
EDAT- 2012/01/24 06:00
MHDA- 2012/04/05 06:00
PMCR- 2014/05/20
CRDT- 2012/01/24 06:00
PHST- 2011/10/21 00:00 [received]
PHST- 2011/12/12 00:00 [accepted]
PHST- 2012/01/24 06:00 [entrez]
PHST- 2012/01/24 06:00 [pubmed]
PHST- 2012/04/05 06:00 [medline]
PHST- 2014/05/20 00:00 [pmc-release]
AID - ni.2210 [pii]
AID - 10.1038/ni.2210 [doi]
PST - epublish
SO  - Nat Immunol. 2012 Jan 22;13(3):300-7. doi: 10.1038/ni.2210.