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

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.

PMID:
24177426
PMCID:
PMC3859399
DOI:
10.1172/JCI70972
[Indexed for MEDLINE]
Free PMC Article

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