Apoptosis of malignant human B cells by ligation of CD20 with monoclonal antibodies

Blood. 1998 Mar 1;91(5):1644-52.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies, Anti-Idiotypic / pharmacology
  • Antibodies, Monoclonal / pharmacology*
  • Antigens, CD20 / immunology
  • Antigens, CD20 / physiology*
  • Apoptosis*
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / physiology
  • Burkitt Lymphoma / pathology*
  • Calcium / metabolism
  • Cell Cycle
  • Cell Division
  • Chelating Agents / pharmacology
  • Cross-Linking Reagents
  • Egtazic Acid / analogs & derivatives
  • Egtazic Acid / pharmacology
  • Goats
  • Humans
  • Mice
  • Receptors, Fc / physiology
  • Tumor Cells, Cultured

Substances

  • Antibodies, Anti-Idiotypic
  • Antibodies, Monoclonal
  • Antigens, CD20
  • Chelating Agents
  • Cross-Linking Reagents
  • Receptors, Fc
  • Egtazic Acid
  • 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid
  • Calcium