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Blood, 1 December 2007, Vol. 110, No. 12, pp. 3978-3984. Prepublished online as a Blood First Edition Paper on August 24, 2007; DOI 10.1182/blood-2007-05-091306. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2007-05-091306v1 110/12/3978    most recent Alert me when this article is cited Alert me if a correction is posted 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 Fischer, S. F Articles by Strasser, A. Search for Related Content PubMed PubMed Citation Articles by Fischer, S. F Articles by Strasser, A. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted May 23, 2007 Accepted August 13, 2007 Pro-apoptotic BH3-only protein Bim is essential for developmentally programmed death of germinal center-derived memory B cells and antibody forming cells Silke F Fischer, Philippe Bouillet, Kristy O'Donnell, Amanda Light, David M Tarlinton, and Andreas Strasser* Department of Molecular Genetics of Cancer, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia Department of Immunology, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia * Corresponding author; email: strasser{at}wehi.edu.au. T cell-dependent B cell immune responses induce germinal centers (GC) that are sites for expansion, diversification and selection of antigen-specific B cells. During the immune response antigen-specific B cells are removed in a process that favours the retention of cells with improved affinity for antigen, a cell death process inhibited by excess Bcl-2. Here we examined the role of the BH3-only protein Bim, an initiator of apoptosis in the Bcl-2-regulated pathway, in the programmed cell death accompanying an immune response. Following immunization, Bim-deficient mice showed persistence of both memory B cells lacking affinity-enhancing mutations in their immunoglobulin genes and antibody forming cells secreting low affinity antibodies. This was accompanied by enhanced survival of both cell types in culture. These results identify for the first time the physiological mechanisms for killing low affinity antibody expressing B cells in an immune response and show this to be dependent on the BH3-only protein Bim. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. R. L. Beishuizen, N. A. M. Kragten, L. Boon, M. A. Nolte, R. A. W. van Lier, and K. P. J. M. van Gisbergen Chronic CD70-Driven Costimulation Impairs IgG Responses by Instructing T Cells to Inhibit Germinal Center B Cell Formation through FasL-Fas Interactions J. Immunol., November 15, 2009; 183(10): 6442 - 6451. [Abstract] [Full Text] [PDF] A. Zaheen, B. Boulianne, J.-Y. Parsa, S. Ramachandran, J. L. Gommerman, and A. Martin AID constrains germinal center size by rendering B cells susceptible to apoptosis Blood, July 16, 2009; 114(3): 547 - 554. [Abstract] [Full Text] [PDF] L. A. O'Reilly, E. A. Kruse, H. Puthalakath, P. N. Kelly, T. Kaufmann, D. C. S. Huang, and A. Strasser MEK/ERK-Mediated Phosphorylation of Bim Is Required to Ensure Survival of T and B Lymphocytes during Mitogenic Stimulation J. Immunol., July 1, 2009; 183(1): 261 - 269. [Abstract] [Full Text] [PDF] J. C. Reed Bcl-2-family proteins and hematologic malignancies: history and future prospects Blood, April 1, 2008; 111(7): 3322 - 3330. [Abstract] [Full Text] [PDF]

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