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Blood, 15 October 2006, Vol. 108, No. 8, pp. 2712-2719. Prepublished online as a Blood First Edition Paper on June 29, 2006; DOI 10.1182/blood-2006-03-014001. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2006-03-014001v1 108/8/2712    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 Jahrsdorfer, B. Articles by Weiner, G. J Search for Related Content PubMed PubMed Citation Articles by Jahrsdorfer, B. Articles by Weiner, G. J Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 30, 2006 Accepted June 13, 2006 B-Chronic Lymphocytic Leukemia Cells and other B cells can produce Granzyme B and gain cytotoxic potential after Interleukin-21-based activation Bernd Jahrsdorfer, Sue E Blackwell, James E Wooldridge, Jian Huang, Melinda W Andreski, Laura S Jacobus, Christiana M Taylor, and George J Weiner* Holden Comprehensive Cancer Center, University of Iowa, USA Department of Statistics, University of Iowa, USA * Corresponding author; email: george-weiner{at}uiowa.edu. B cells are not currently viewed as being capable of producing granzyme B or being cytotoxic. We found that B-Chronic Lymphocytic Leukemia (B-CLL) cells treated with Interleukin 21 (IL-21) produce low levels of granzyme B. The addition of either CpG ODN or anti-B cell receptor antibody (anti-BCR) to IL-21 results in enhanced production of functional granzyme B by B-CLL cells. B-CLL cells treated with IL-21 and CpG ODN undergo apoptosis and are able to induce apoptosis of untreated bystander B-CLL cells. This effect can be inhibited by anti-Granzyme B antibody. Benign human B cells, EBV-tranformed lymphoblasts, and many standard lymphoma cell lines produce high levels of granzyme B in response to IL-21 and anti-BCR. Our results suggest the ability to induce production of functional Granzyme B by B cells could open new approaches to the therapy of B-CLL and other B cell malignancies. Our findings also have significant implications on our understanding of the role of B cells for immune regulation and for a variety of immune phenomena including cancer immunity, autoimmunity and infectious immunity. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. Xie, H. Bai, L. Liu, X. Xie, J. Ayello, X. Ma, and J. Zhang Apoptosis of lymphocytes and monocytes infected with influenza virus might be the mechanism of combating virus and causing secondary infection by influenza Int. Immunol., November 1, 2009; 21(11): 1251 - 1262. [Abstract] [Full Text] [PDF] M. Hagn, E. Schwesinger, V. Ebel, K. Sontheimer, J. Maier, T. Beyer, T. Syrovets, Y. Laumonnier, D. Fabricius, T. Simmet, et al. Human B Cells Secrete Granzyme B When Recognizing Viral Antigens in the Context of the Acute Phase Cytokine IL-21 J. Immunol., August 1, 2009; 183(3): 1838 - 1845. [Abstract] [Full Text] [PDF] C. S. Hinrichs, R. Spolski, C. M. Paulos, L. Gattinoni, K. W. Kerstann, D. C. Palmer, C. A. Klebanoff, S. A. Rosenberg, W. J. Leonard, and N. P. Restifo IL-2 and IL-21 confer opposing differentiation programs to CD8+ T cells for adoptive immunotherapy Blood, June 1, 2008; 111(11): 5326 - 5333. [Abstract] [Full Text] [PDF] D. de Totero, R. Meazza, M. Capaia, M. Fabbi, B. Azzarone, E. Balleari, M. Gobbi, G. Cutrona, M. Ferrarini, and S. Ferrini The opposite effects of IL-15 and IL-21 on CLL B cells correlate with differential activation of the JAK/STAT and ERK1/2 pathways Blood, January 15, 2008; 111(2): 517 - 524. [Abstract] [Full Text] [PDF]

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