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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.

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