The mechanism of anti-CD20-mediated B cell depletion revealed by intravital imaging

J Clin Invest. 2013 Dec;123(12):5098-103. doi: 10.1172/JCI70972. Epub 2013 Nov 1.


Anti-CD20 Ab therapy has proven successful for treating B cell malignancies and a number of autoimmune diseases. However, how anti-CD20 Abs operate in vivo to mediate B cell depletion is not fully understood. In particular, the anatomical location, the type of effector cells, and the mechanism underlying anti-CD20 therapy remain uncertain. Here, we found that the liver is a major site for B cell depletion and that recirculation accounts for the decrease in B cell numbers observed in secondary lymphoid organs. Using intravital imaging, we established that, upon anti-CD20 treatment, Kupffer cells (KCs) mediate the abrupt arrest and subsequent engulfment of B cells circulating in the liver sinusoids. KCs were also effective in depleting malignant B cells in a model of spontaneous lymphoma. Our results identify Ab-dependent cellular phagocytosis by KCs as a primary mechanism of anti-CD20 therapy and provide an experimental framework for optimizing the efficacy of therapeutic Abs.

Publication types

  • Research Support, Non-U.S. Gov't
  • Video-Audio Media

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / therapeutic use*
  • Antigens, CD20 / immunology*
  • B-Lymphocytes / pathology*
  • Burkitt Lymphoma
  • Clodronic Acid / pharmacology
  • Disease Models, Animal
  • Fluorescent Dyes
  • Kupffer Cells / physiology*
  • Kupffer Cells / ultrastructure
  • Liposomes
  • Liver / immunology*
  • Liver Regeneration
  • Lymphocyte Depletion*
  • Lymphoid Tissue / pathology
  • Lymphoma, B-Cell / pathology
  • Lymphoma, B-Cell / therapy*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Optical Imaging / methods*
  • Phagocytosis


  • Antibodies, Monoclonal
  • Antigens, CD20
  • Fluorescent Dyes
  • Liposomes
  • Clodronic Acid