title: Rituximab inhibits Kv1.3 channels in human B lymphoma cells via activation of FcγRIIB receptors.
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.
authors.affiliation: Department of Neurology, the Second Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang 150086, People's Republic of China.
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Wang
authors.forename: Ning
authors.initials: N
authors.lastname: Wang
authors.forename: Xiao-Yu
authors.initials: XY
authors.lastname: Lu
authors.forename: Bing-Chen
authors.initials: BC
authors.lastname: Liu
authors.forename: Murali K
authors.initials: MK
authors.lastname: Yanda
authors.forename: John Z
authors.initials: JZ
authors.lastname: Song
authors.forename: Helena M
authors.initials: HM
authors.lastname: Dai
authors.forename: Yu-Liang
authors.initials: YL
authors.lastname: Sun
authors.forename: Hui-Fang
authors.initials: HF
authors.lastname: Bao
authors.forename: Douglas C
authors.initials: DC
authors.lastname: Eaton
authors.forename: He-Ping
authors.initials: HP
authors.lastname: Ma
mesh_terms: D000276:Adjuvants, Immunologic / Q000378:metabolism; D000818:Animals; D058846:Antibodies, Monoclonal, Murine-Derived / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000378:metabolism*; D045744:Cell Line, Tumor; D002772:Cholera Toxin; D006801:Humans; D051664:Kv1.3 Potassium Channel / Q000378:metabolism*; D016393:Lymphoma, B-Cell / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000378:metabolism; D011803:Quinine / Q000378:metabolism; D017452:Receptors, IgG / Q000378:metabolism*; D000069283:Rituximab
chemical_list: D000276:Adjuvants, Immunologic; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; C499173:FCGR2B protein, human; D051664:Kv1.3 Potassium Channel; D026902:Potassium Channel Blockers; D017452:Receptors, IgG; D000069283:Rituximab; D002772:Cholera Toxin; D011803:Quinine