The mechanism of anti-CD20–mediated B cell depletion revealed by intravital imaging
Fabricio Montalvao, … , Nico Van Rooijen, Philippe Bousso
Fabricio Montalvao, … , Nico Van Rooijen, Philippe Bousso
Published December 2, 2013; First published November 1, 2013
Citation Information: J Clin Invest. 2013;123(12):5098-5103. https://doi.org/10.1172/JCI70972.
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Brief Report Immunology

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

Abstract

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.

Authors

Fabricio Montalvao, Zacarias Garcia, Susanna Celli, Béatrice Breart, Jacques Deguine, Nico Van Rooijen, Philippe Bousso

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