Referenced in: none

Automatically associated channels: Kv1.3

Title: Rituximab inhibits Kv1.3 channels in human B lymphoma cells via activation of FcγRIIB receptors.

Authors: Li-Hua Wang, Ning Wang, Xiao-Yu Lu, Bing-Chen Liu, Murali K Yanda, John Z Song, Helena M Dai, Yu-Liang Sun, Hui-Fang Bao, Douglas C Eaton, He-Ping Ma

Journal, date & volume: Biochim. Biophys. Acta, 2012 Feb , 1823, 505-13

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/22192444

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.