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
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共 47 条
  • [1] Ligand-independent signaling functions for the B lymphocyte antigen receptor and their role in positive selection during B lymphopoiesis
    Bannish, G
    Fuentes-Pananá, EM
    Cambier, JC
    Pear, WS
    Monroe, JG
    [J]. 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
    Bell, Andrew I.
    Groves, Katherine
    Kelly, Gemma L.
    Croom-Carter, Debbie
    Hui, Edwin
    Chan, Anthony T. C.
    Rickinson, Alan B.
    [J]. JOURNAL OF GENERAL VIROLOGY, 2006, 87 : 2885 - 2890
  • [3] AN EPSTEIN-BARR-VIRUS TRANSFORMATION-ASSOCIATED MEMBRANE-PROTEIN INTERACTS WITH SRC FAMILY TYROSINE KINASES
    BURKHARDT, AL
    BOLEN, JB
    KIEFF, E
    LONGNECKER, R
    [J]. 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
    Caldwell, RG
    Brown, RG
    Longnecker, R
    [J]. 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
    Caldwell, RG
    Wilson, JB
    Anderson, SJ
    Longnecker, R
    [J]. IMMUNITY, 1998, 9 (03) : 405 - 411
  • [6] Epstein-Barr virus latent membrane protein 2A regulates c-Jun protein through extracellular signal-regulated kinase
    Chen, SY
    Lu, J
    Shih, YC
    Tsai, CH
    [J]. 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
    Corcoran, AE
    Smart, FM
    Cowling, RJ
    Crompton, T
    Owen, MJ
    Venkitaraman, AR
    [J]. EMBO JOURNAL, 1996, 15 (08) : 1924 - 1932
  • [8] Generation and characterization of stromal cell independent IL-7 dependent B cell lines
    Corfe, Steven A.
    Gray, Alice P.
    Paige, Christopher J.
    [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
    ERA, T
    OGAWA, M
    NISHIKAWA, SI
    OKAMOTO, M
    HONJO, T
    AKAGI, K
    MIYAZAKI, JI
    YAMAMURA, KI
    [J]. EMBO JOURNAL, 1991, 10 (02) : 337 - 342
  • [10] Frequent aberrant immunoglobulin gene rearrangements in pro-B cells revealed by a bcl-x(L) transgene
    Fang, W
    Mueller, DL
    Pennell, CA
    Rivard, JJ
    Li, YS
    Hardy, RR
    Schlissel, MS
    Behrens, TW
    [J]. IMMUNITY, 1996, 4 (03) : 291 - 299