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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 Mongini, P. K.A. Articles by Inman, J. K. Search for Related Content PubMed PubMed Citation Articles by Mongini, P. K.A. Articles by Inman, J. K. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, Vol. 92 No. 10 (November 15), 1998: pp. 3756-3771 Evidence for an Upper Affinity Threshold for Anti-IgM-Induced Apoptosis in a Human B-Cell Lymphoma Patricia K.A. Mongini, Qingyang Liu, Maria A. Vilensky, Patricia F. Highet, and John K. Inman From the Department of Rheumatology, Hospital for Joint Diseases, New York, NY; the Department of Pathology, Kaplan Comprehensive Cancer Center, New York University School of Medicine, New York, NY; and the Laboratory of Immunology, National Institutes of Health, Bethesda, MD. The influence of ligand:receptor affinity on B-cell antigen receptor (BCR)-induced apoptosis in the IgM+ Burkitt lymphoma line, Ramos, was evaluated with a group of affinity-diverse murine monoclonal antibodies (MoAbs) specific for human B-cell IgM. The studies showed not only a minimal affinity threshold for the induction of apoptosis, but, interestingly, also a maximal affinity threshold above which increases in affinity were associated with diminished apoptosis. The lesser capacity of high-affinity MoAb to induce apoptosis was paralleled by a lesser capacity to induce receptor cross-linking. At high ligand concentration, high MoAb affinity was also associated with a diminished capacity to induce early protein tyrosine phosphorylation. The compromised capacity of two high-affinity MoAbs to trigger apoptosis may be, at least in part, explained by two separate phenomena that can impair the formation of mIgM cross-links: (1) more stable univalent binding and (2) a tendency for monogamous binding of both MoAb Fab to two Fab epitopes on mIgM. These in vitro studies suggest that the use of the highest affinity MoAbs for antireceptor immunotherapies that depend on receptor cross-linking might, on occasion, be contraindicated. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. S. Goodyear and G. J. Silverman Death by a B Cell Superantigen: In Vivo VH-targeted Apoptotic Supraclonal B Cell Deletion by a Staphylococcal Toxin J. Exp. Med., May 5, 2003; 197(9): 1125 - 1139. [Abstract] [Full Text] [PDF]

	Copyright © 1998 by American Society of Hematology         Online ISSN: 1528-0020