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Author Notes:

Correspondence: H.-P. Ma, Department of Physiology, Emory University School of Medicine, 615 Michael ST, Suite 601, Atlanta, GA 30322, USA; Tel.: +1 404 727 0617; Fax: +1 404 727 0329; Email: heping.ma@emory.edu

Authors' Contributions: LHW, NW, XYL, and BCL contributed equally to this work.

Acknowledgments: We thank Dr. David G. Warnock (University of Alabama at Birmingham) for his idea to initiate this study.

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Research Funding:

This work was supported by Department of Health and Human Services, National Institutes of Health grants (5R01-DK067110 to He-Ping Ma and 5R37-DK037963 to Douglas C. Eaton).

Keywords:

  • Voltage-dependent potassium channel
  • Fc receptor
  • Rituximab
  • Apoptosis
  • Patch-clamp technique
  • Confocal microscopy

Rituximab inhibits Kv1.3 channels in human B lymphoma cells via activation of FcyRIIB receptors

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Journal Title:

BBA - Molecular Cell Research

Volume:

Volume 1823, Number 2

Publisher:

, Pages 505-513

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Kv1.3 channels play an important role in modulating lymphocyte proliferation and apoptosis. We hypothesized that Kv1.3 channels in B lymphocytes might be regulated by rituximab, an antibody to CD20, a drug for treatments of B-cell lymphomas and autoimmune diseases. Using both whole-cell and cell-attached patch-clamp techniques, we found that rituximab inhibited Kv1.3 channels in Daudi human B lymphoma cells by promoting the channel inactivation at a concentration which was much greater than that required for activation of CD20. The effect of rituximab on Kv1.3 channels was abolished after selective blockade of FcγRIIB receptors with anti-FcγRIIB antibody. Western blot experiments showed that Daudi B cells expressed both Kv1.3 channel and the low affinity Fc receptor, FcγRIIB, which could be activated by the Fc region of rituximab. In contrast, normal lymphocytes expressed less Kv1.3 channels with faster inactivation. Confocal microscopy and flow cytometry data showed that rituximab induced apoptosis of Daudi B cells and that the effect was attenuated by blockade of FcγRIIB receptors and partially mimicked by inhibition of Kv1.3 channels. These results suggest that in addition to previously described complement-dependent cytotoxicity, rituximab also induces apoptosis of malignant B lymphocyte by stimulating FcγRIIB receptors and inhibiting Kv1.3 channels.

Copyright information:

© 2011 Elsevier B.V. All rights reserved.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported License (http://creativecommons.org/licenses/by-nc-nd/3.0/).

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