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Blood, 1 January 2004, Vol. 103, No. 1, pp. 168-176. Prepublished online as a Blood First Edition Paper on September 11, 2003; DOI 10.1182/blood-2003-07-2473. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-07-2473v1 103/1/168    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Katz, E. Articles by Harnett, M. M. Search for Related Content PubMed PubMed Citation Articles by Katz, E. Articles by Harnett, M. M. Related Collections Immunobiology Apoptosis Cell Cycle Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Bcl-xL antagonism of BCR-coupled mitochondrial phospholipase A2 signaling correlates with protection from apoptosis in WEHI-231 B cells Elad Katz, Caroline Lord, Catriona A. Ford, Stephen B. Gauld, Natalie A. Carter, and Margaret M. Harnett From the Division of Immunology, Infection and Inflammation, University of Glasgow, Glasgow, United Kingdom Crosslinking of the antigen receptors on the immature B-cell lymphoma, WEHI-231, leads to growth arrest and apoptosis. Commitment to such B-cell receptor (BCR)–mediated apoptosis correlates with mitochondrial phospholipase A2 activation, disruption of mitochondrial function, and cathepsin B activation. CD40 signaling has been reported to rescue WEHI-231 B cells from BCR-driven apoptosis primarily via up-regulation of the antiapoptotic protein Bcl-xL. Coupling of the BCR to the mitochondrial phospholipase A2–dependent apoptotic pathway can be prevented by rescue signals via CD40. We now show that overexpression of Bcl-xL can prevent mitochondrial phospholipase A2 activation, disruption of mitochondrial potential, and postmitochondrial execution of BCR-mediated apoptosis via cathepsin B activation. Moreover, overexpression of Bcl-xL protects WEHI-231 B cells from mitochondrial disruption and apoptosis resulting from culture with exogenous arachidonic acid, the product of phospholipase A2 action, suggesting that Bcl-xL may act to antagonize arachidonic acid–mediated disruption of mitochondrial integrity. However, although Bcl-xL expression can mimic CD40-mediated rescue of BCR-driven apoptosis, it cannot substitute for CD40 signaling in the reversal of BCR-mediated growth arrest of WEHI-231 B cells. Rather, CD40 signaling additionally induces conversion of arachidonic acid to prostaglandin E2 (PGE2), which promotes WEHI-231 B-cell proliferation by restoring the sustained, cycling extracellular signal–regulated/mitogen-activated protein kinase (ErkMAPkinase) signaling required for cell cycle progression. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Poggianella, M. Bestagno, and O. R. Burrone The Extracellular Membrane-Proximal Domain of Human Membrane IgE Controls Apoptotic Signaling of the B Cell Receptor in the Mature B Cell Line A20 J. Immunol., September 15, 2006; 177(6): 3597 - 3605. [Abstract] [Full Text] [PDF] S. Kirschnek and E. Gulbins Phospholipase A2 Functions in Pseudomonas aeruginosa- Induced Apoptosis Infect. Immun., February 1, 2006; 74(2): 850 - 860. [Abstract] [Full Text] [PDF] J. He, Y. Tohyama, K.-i. Yamamoto, M. Kobayashi, Y. Shi, T. Takano, C. Noda, K. Tohyama, and H. Yamamura Lysosome is a primary organelle in B cell receptor-mediated apoptosis: an indispensable role of Syk in lysosomal function Genes Cells, January 1, 2005; 10(1): 23 - 35. [Abstract] [Full Text] [PDF] M. M. Harnett CD40: A Growing Cytoplasmic Tale Sci. Signal., June 15, 2004; 2004(237): pe25 - pe25. [Abstract] [Full Text] [PDF]

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