EBV LMP2A provides a surrogate pre-B cell receptor signal through constitutive activation of the ERK/MAPK pathway

被引:39
作者
Anderson, Leah J. [1 ]
Longnecker, Richard [1 ]
机构
[1] Northwestern Univ, Dept Microbiol & Immunol, Chicago, IL 60611 USA
关键词
D O I
10.1099/vir.0.2008/001461-0
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Latent membrane protein 2A (LMP2A) of Epstein-Barr virus (EBV) provides developmental and survival signals that mimic those of a B-cell receptor (BCR). Expression of LMP2A during B-cell development results in the ability of B cells to exit the bone marrow in the absence of a BCR and persist in the periphery, where they would normally undergo apoptosis. This study extends the current knowledge of LMP2A function by examining the growth properties of bone marrow B cells from TgE LMP2A mice. Despite the lack of pre-BCR expression, bone marrow B cells from TgE LMP2A mice proliferate and survive in low concentrations of interleukin 7, similar to wild-type cells. Constitutive phosphorylation of ERK/MAPK and PI3K/Akt in TgE LMP2A bone marrow B cells is also reminiscent of signalling through the pre-BCR, altogether demonstrating that LMP2A provides a pre-BCR-like signal to developing B cells.
引用
收藏
页码:1563 / 1568
页数:6
相关论文
共 47 条
[1]   Ligand-independent signaling functions for the B lymphocyte antigen receptor and their role in positive selection during B lymphopoiesis [J].
Bannish, G ;
Fuentes-Pananá, EM ;
Cambier, JC ;
Pear, WS ;
Monroe, JG .
JOURNAL OF EXPERIMENTAL MEDICINE, 2001, 194 (11) :1583-1596
[2]   Analysis of Epstein-Barr virus latent gene expression in endemic Burkitt's lymphoma and nasopharyngeal carcinoma tumour cells by using quantitative real-time PCR assays [J].
Bell, Andrew I. ;
Groves, Katherine ;
Kelly, Gemma L. ;
Croom-Carter, Debbie ;
Hui, Edwin ;
Chan, Anthony T. C. ;
Rickinson, Alan B. .
JOURNAL OF GENERAL VIROLOGY, 2006, 87 :2885-2890
[3]   AN EPSTEIN-BARR-VIRUS TRANSFORMATION-ASSOCIATED MEMBRANE-PROTEIN INTERACTS WITH SRC FAMILY TYROSINE KINASES [J].
BURKHARDT, AL ;
BOLEN, JB ;
KIEFF, E ;
LONGNECKER, R .
JOURNAL OF VIROLOGY, 1992, 66 (08) :5161-5167
[4]   Epstein-Barr virus LMP2A-induced B-cell survival in two unique classes of EμLMP2A transgenic mice [J].
Caldwell, RG ;
Brown, RG ;
Longnecker, R .
JOURNAL OF VIROLOGY, 2000, 74 (03) :1101-1113
[5]   Epstein-Barr virus LMP2A drives B cell development and survival in the absence of normal B cell receptor signals [J].
Caldwell, RG ;
Wilson, JB ;
Anderson, SJ ;
Longnecker, R .
IMMUNITY, 1998, 9 (03) :405-411
[6]   Epstein-Barr virus latent membrane protein 2A regulates c-Jun protein through extracellular signal-regulated kinase [J].
Chen, SY ;
Lu, J ;
Shih, YC ;
Tsai, CH .
JOURNAL OF VIROLOGY, 2002, 76 (18) :9556-9561
[7]   The interleukin-7 receptor alpha chain transmits distinct signals for proliferation and differentiation during B lymphopoiesis [J].
Corcoran, AE ;
Smart, FM ;
Cowling, RJ ;
Crompton, T ;
Owen, MJ ;
Venkitaraman, AR .
EMBO JOURNAL, 1996, 15 (08) :1924-1932
[8]   Generation and characterization of stromal cell independent IL-7 dependent B cell lines [J].
Corfe, Steven A. ;
Gray, Alice P. ;
Paige, Christopher J. .
JOURNAL OF IMMUNOLOGICAL METHODS, 2007, 325 (1-2) :9-19
[9]   DIFFERENTIATION OF GROWTH SIGNAL REQUIREMENT OF LYMPHOCYTE-B PRECURSOR IS DIRECTED BY EXPRESSION OF IMMUNOGLOBULIN [J].
ERA, T ;
OGAWA, M ;
NISHIKAWA, SI ;
OKAMOTO, M ;
HONJO, T ;
AKAGI, K ;
MIYAZAKI, JI ;
YAMAMURA, KI .
EMBO JOURNAL, 1991, 10 (02) :337-342
[10]   Frequent aberrant immunoglobulin gene rearrangements in pro-B cells revealed by a bcl-x(L) transgene [J].
Fang, W ;
Mueller, DL ;
Pennell, CA ;
Rivard, JJ ;
Li, YS ;
Hardy, RR ;
Schlissel, MS ;
Behrens, TW .
IMMUNITY, 1996, 4 (03) :291-299