PI3 Kinase Signals BCR-Dependent Mature B Cell Survival

Lakshmi Srinivasan; Yoshiteru Sasaki; Dinis Pedro Calado; Baochun Zhang; Ji Hye Paik; Ronald A. DePinho; Jeffrey L. Kutok; John F. Kearney; Kevin L. Otipoby; Klaus Rajewsky

doi:10.1016/j.cell.2009.08.041

PI3 Kinase Signals BCR-Dependent Mature B Cell Survival

Lakshmi Srinivasan
, Yoshiteru Sasaki
, Dinis Pedro Calado
, Baochun Zhang
, Ji Hye Paik
, Ronald A. DePinho
, Jeffrey L. Kutok
, John F. Kearney
, Kevin L. Otipoby
, Klaus Rajewsky

Research output: Contribution to journal › Article › peer-review

591 Scopus citations

Abstract

Previous work has shown that mature B cells depend upon survival signals delivered to the cells by their antigen receptor (BCR). To identify the molecular nature of this survival signal, we have developed a genetic approach in which ablation of the BCR is combined with the activation of specific, BCR dependent signaling cascades in mature B cells in vivo. Using this system, we provide evidence that the survival of BCR deficient mature B cells can be rescued by a single signaling pathway downstream of the BCR, namely PI3K signaling, with the FOXO1 transcription factor playing a central role.

Original language	English (US)
Pages (from-to)	573-586
Number of pages	14
Journal	Cell
Volume	139
Issue number	3
DOIs	https://doi.org/10.1016/j.cell.2009.08.041
State	Published - Oct 30 2009
Externally published	Yes

Keywords

MOLIMMUNO
SIGNALING

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

Access to Document

10.1016/j.cell.2009.08.041

Cite this

@article{271b4b1ed92d4596ab8a3eb5658c30b3,

title = "PI3 Kinase Signals BCR-Dependent Mature B Cell Survival",

abstract = "Previous work has shown that mature B cells depend upon survival signals delivered to the cells by their antigen receptor (BCR). To identify the molecular nature of this survival signal, we have developed a genetic approach in which ablation of the BCR is combined with the activation of specific, BCR dependent signaling cascades in mature B cells in vivo. Using this system, we provide evidence that the survival of BCR deficient mature B cells can be rescued by a single signaling pathway downstream of the BCR, namely PI3K signaling, with the FOXO1 transcription factor playing a central role.",

keywords = "MOLIMMUNO, SIGNALING",

author = "Lakshmi Srinivasan and Yoshiteru Sasaki and Calado, \{Dinis Pedro\} and Baochun Zhang and Paik, \{Ji Hye\} and DePinho, \{Ronald A.\} and Kutok, \{Jeffrey L.\} and Kearney, \{John F.\} and Otipoby, \{Kevin L.\} and Klaus Rajewsky",

note = "Funding Information: We thank D. Ghitza, A. Pellerin, A. Monti, A.Tetreault, J. Grundy, J. Wang, J. Xia and W.F. Jia for expert technical assistance; E. Derudder for reagents; all Rajewsky lab members for discussions; and M. Janz for critical reading of the manuscript; A. Klippel for the MP110 ∗ cDNA; and K. Kaibuchi for Rac1DA cDNA. K.R. is supported by NIH grants AI054636 and CA092625, the Leukemia and Lymphoma Society and the European Union through MUGEN; L.S. by the T32 training grant of the Joint Program in Hematology and Transfusion Medicine at Harvard Medical School; J.F.K. by NIH grant AI014782-31; D.P.C. by a postdoctoral fellowship from the Portuguese Foundation for Science and Technology (FCT-MCES); B.Z. by a postdoctoral fellowship of the Leukemia and Lymphoma Society; and RAD by the NIH and the Robert A. and Renee E. Belfer Foundation. ",

year = "2009",

month = oct,

day = "30",

doi = "10.1016/j.cell.2009.08.041",

language = "English (US)",

volume = "139",

pages = "573--586",

journal = "Cell",

issn = "0092-8674",

publisher = "Elsevier B.V.",

number = "3",

}

TY - JOUR

T1 - PI3 Kinase Signals BCR-Dependent Mature B Cell Survival

AU - Srinivasan, Lakshmi

AU - Sasaki, Yoshiteru

AU - Calado, Dinis Pedro

AU - Zhang, Baochun

AU - Paik, Ji Hye

AU - DePinho, Ronald A.

AU - Kutok, Jeffrey L.

AU - Kearney, John F.

AU - Otipoby, Kevin L.

AU - Rajewsky, Klaus

N1 - Funding Information: We thank D. Ghitza, A. Pellerin, A. Monti, A.Tetreault, J. Grundy, J. Wang, J. Xia and W.F. Jia for expert technical assistance; E. Derudder for reagents; all Rajewsky lab members for discussions; and M. Janz for critical reading of the manuscript; A. Klippel for the MP110 ∗ cDNA; and K. Kaibuchi for Rac1DA cDNA. K.R. is supported by NIH grants AI054636 and CA092625, the Leukemia and Lymphoma Society and the European Union through MUGEN; L.S. by the T32 training grant of the Joint Program in Hematology and Transfusion Medicine at Harvard Medical School; J.F.K. by NIH grant AI014782-31; D.P.C. by a postdoctoral fellowship from the Portuguese Foundation for Science and Technology (FCT-MCES); B.Z. by a postdoctoral fellowship of the Leukemia and Lymphoma Society; and RAD by the NIH and the Robert A. and Renee E. Belfer Foundation.

PY - 2009/10/30

Y1 - 2009/10/30

N2 - Previous work has shown that mature B cells depend upon survival signals delivered to the cells by their antigen receptor (BCR). To identify the molecular nature of this survival signal, we have developed a genetic approach in which ablation of the BCR is combined with the activation of specific, BCR dependent signaling cascades in mature B cells in vivo. Using this system, we provide evidence that the survival of BCR deficient mature B cells can be rescued by a single signaling pathway downstream of the BCR, namely PI3K signaling, with the FOXO1 transcription factor playing a central role.

AB - Previous work has shown that mature B cells depend upon survival signals delivered to the cells by their antigen receptor (BCR). To identify the molecular nature of this survival signal, we have developed a genetic approach in which ablation of the BCR is combined with the activation of specific, BCR dependent signaling cascades in mature B cells in vivo. Using this system, we provide evidence that the survival of BCR deficient mature B cells can be rescued by a single signaling pathway downstream of the BCR, namely PI3K signaling, with the FOXO1 transcription factor playing a central role.

KW - MOLIMMUNO

KW - SIGNALING

UR - https://www.scopus.com/pages/publications/70350304558

UR - https://www.scopus.com/pages/publications/70350304558#tab=citedBy

U2 - 10.1016/j.cell.2009.08.041

DO - 10.1016/j.cell.2009.08.041

M3 - Article

C2 - 19879843

AN - SCOPUS:70350304558

SN - 0092-8674

VL - 139

SP - 573

EP - 586

JO - Cell

JF - Cell

IS - 3

ER -

PI3 Kinase Signals BCR-Dependent Mature B Cell Survival

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this