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Prepublished online as a Blood First Edition Paper on September 19, 2002; DOI 10.1182/blood-2002-06-1761. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-06-1761v1 101/3/1045    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 Cragg, M. S. Articles by Glennie, M. J. Search for Related Content PubMed PubMed Citation Articles by Cragg, M. S. Articles by Glennie, M. J. Related Collections Immunobiology Neoplasia Immunotherapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 February 2003, Vol. 101, No. 3, pp. 1045-1052 IMMUNOBIOLOGY Complement-mediated lysis by anti-CD20 mAb correlates with segregation into lipid rafts Mark S. Cragg, Suzanne M. Morgan, H. T. Claude Chan, B. Paul Morgan, A. V. Filatov, Peter W. M. Johnson, Ruth R. French, and Martin J. Glennie From the Tenovus Research Laboratory and Medical Oncology, Cancer Sciences Division, School of Medicine, General Hospital, Southampton, United Kingdom; University of Wales, Department of Medical Biochemistry, College of Medicine, Heath Park, Cardiff, United Kingdom; Institute of Immunology Kashirskoye Shosse, Moscow, Russia. Despite the clinical success of anti-CD20 monoclonal antibody (mAb) in the treatment of lymphoma, there remains considerable uncertainty about its mechanism of action. Here we show that the ability of mAbs to translocate CD20 into low-density, detergent-insoluble membrane rafts appears to control how effectively they mediate complement lysis of lymphoma cells. In vitro studies using a panel of anti-B-cell mAbs revealed that the anti-CD20 mAbs, with one exception (B1), are unusually effective at recruiting human complement. Differences in complement recruitment could not be explained by the level of mAb binding or isotype but did correlate with the redistribution of CD20 in the cell membrane following mAb ligation. Membrane fractionation confirmed that B1, unlike 1F5 and rituximab, was unable to translocate CD20 into lipid rafts. In addition, we were able to drive B1 and a range of other anti-B-cell mAbs into a detergent-insoluble fraction of the cell by hyper-cross-linking with an F(ab')2 anti-Ig Ab, a treatment that also conferred the ability to activate lytic complement. Thus, we have shown that an important mAb effector function appears to be controlled by movement of the target molecule into membrane rafts, either because a raft location favors complement activation by mAbs or because rafts are more sensitive to complement penetration. © 2003 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: T. M. Illidge, M. Bayne, N. S. Brown, S. Chilton, M. S. Cragg, M. J. Glennie, Y. Du, V. Lewington, J. Smart, J. Thom, et al. Phase 1/2 study of fractionated 131I-rituximab in low-grade B-cell lymphoma: the effect of prior rituximab dosing and tumor burden on subsequent radioimmunotherapy Blood, February 12, 2009; 113(7): 1412 - 1421. [Abstract] [Full Text] [PDF] S. A. Beers, M. S. Cragg, and M. J. 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