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This Article Full Text Full Text (PDF) 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 Shan, D. Articles by Press, O. W. Search for Related Content PubMed PubMed Citation Articles by Shan, D. Articles by Press, O. W. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Apoptosis of Malignant Human B Cells by Ligation of CD20 With Monoclonal Antibodies Daming Shan, Jeffrey A. Ledbetter, and Oliver W. Press From the Departments of Biological Structure and Medicine of the University of Washington; the Fred Hutchinson Cancer Research Center; and Bristol-Myers Squibb Pharmaceutical Research Institute, Seattle, WA. CD20 is a nonglycosylated 33 to 37 kD phosphoprotein involved in B-cell signaling that subserves important functions in the regulation of B-cell proliferation and differentiation. In addition, this B-cell surface antigen has been shown recently to be an effective target for immunotherapy of B-cell malignancies using chimeric (mouse/human) or radiolabeled murine monoclonal anti-CD20 antibodies. In this report we show that extensive crosslinking of CD20 with murine anti-CD20 monoclonal antibodies (MoAbs) in the presence of either goat anti-mouse IgG or Fc receptor (FcR)-expressing cells directly inhibits B-cell proliferation, induces nuclear DNA fragmentation, and leads to cell death by apoptosis. The apoptotic effects of these MoAbs can be inhibited by chelation of extracellular or intracellular Ca2+ by EGTA or Bapta AM, indicating that anti-CD20-mediated apoptosis may be related to changes in Ca2+ concentration. These findings suggest that ligation of CD20 in vivo by anti-CD20 antibodies in the presence of FcR-expressing cells may initiate signal transduction events that induce elevation of [Ca2+]i and lead to apoptosis of malignant B cells, thereby contributing to the impressive tumor regressions observed in mouse models and clinical trials using anti-CD20 MoAbs. Blood, Vol. 91 No. 5 (March 1), 1998: pp. 1644-1652 © 1998 by The American Society of Hematology. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. S. Hayden-Ledbetter, C. G. Cerveny, E. Espling, W. A. Brady, L. S. Grosmaire, P. Tan, R. Bader, S. Slater, C. A. Nilsson, D. S. Barone, et al. 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Geisler, and J. Jurlander The chimeric anti-CD20 antibody rituximab induces apoptosis in B-cell chronic lymphocytic leukemia cells through a p38 mitogen activated protein-kinase-dependent mechanism Blood, February 15, 2002; 99(4): 1314 - 1319. [Abstract] [Full Text] [PDF] G. Cartron, L. Dacheux, G. Salles, P. Solal-Celigny, P. Bardos, P. Colombat, and H. Watier Therapeutic activity of humanized anti-CD20 monoclonal antibody and polymorphism in IgG Fc receptor Fcgamma RIIIa gene Blood, February 1, 2002; 99(3): 754 - 758. [Abstract] [Full Text] [PDF] J. C. Byrd, S. Kitada, I. W. Flinn, J. L. Aron, M. Pearson, D. Lucas, and J. C. Reed The mechanism of tumor cell clearance by rituximab in vivo in patients with B-cell chronic lymphocytic leukemia: evidence of caspase activation and apoptosis induction Blood, February 1, 2002; 99(3): 1038 - 1043. [Abstract] [Full Text] [PDF] J. Golay, M. Lazzari, V. Facchinetti, S. Bernasconi, G. Borleri, T. Barbui, A. Rambaldi, and M. 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Bonavida Rituximab Inactivates Signal Transducer and Activation of Transcription 3 (STAT3) Activity in B-Non-Hodgkin's Lymphoma through Inhibition of the Interleukin 10 Autocrine/Paracrine Loop and Results in Down-Regulation of Bcl-2 and Sensitization to Cytotoxic Drugs Cancer Res., July 1, 2001; 61(13): 5137 - 5144. [Abstract] [Full Text] [PDF] G. Jung, L. Grosse-Hovest, P. H. Krammer, and H.-G. Rammensee Target Cell-restricted Triggering of the CD95 (APO-1/Fas) Death Receptor with Bispecific Antibody Fragments Cancer Res., March 1, 2001; 61(5): 1846 - 1848. [Abstract] [Full Text] S. Alas, C. Emmanouilides, and B. Bonavida Inhibition of Interleukin 10 by Rituximab Results in Down-Regulation of Bcl-2 and Sensitization of B-cell Non-Hodgkin's Lymphoma to Apoptosis Clin. Cancer Res., March 1, 2001; 7(3): 709 - 723. [Abstract] [Full Text] M.-A. Ghetie, H. Bright, and E. S. Vitetta Homodimers but not monomers of Rituxan (chimeric anti-CD20) induce apoptosis in human B-lymphoma cells and synergize with a chemotherapeutic agent and an immunotoxin Blood, March 1, 2001; 97(5): 1392 - 1398. [Abstract] [Full Text] [PDF] K. S. Kan, V. A. Anderson, W. S. Leong, A. M. Smith, A. T. Worth, and G. T. Stevenson Thioether-Bonded Constructs of Fab'{{gamma}} and Fc{{gamma}} Modules Utilizing Differential Reduction of Interchain Disulfide Bonds J. Immunol., January 15, 2001; 166(2): 1320 - 1326. [Abstract] [Full Text] [PDF] B. Jahrsdörfer, G. Hartmann, E. Racila, W. Jackson, L. Mühlenhoff, G. Meinhardt, S. Endres, B. K. Link, A. M. Krieg, and G. J. Weiner CpG DNA increases primary malignant B cell expression of costimulatory molecules and target antigens J. Leukoc. Biol., January 1, 2001; 69(1): 81 - 88. [Abstract] [Full Text] O. W. Press, J. P. Leonard, B. Coiffier, R. Levy, and J. 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