K+ channel expression during B cell differentiation: implications for immunomodulation and autoimmunity.
Using whole-cell patch-clamp, fluorescence microscopy and flow cytometry, we demonstrate a switch in potassium channel expression during differentiation of human B cells from naive to memory cells. Naive and IgD(+)CD27(+) memory B cells express small numbers of the voltage-gated Kv1.3 and the Ca(2+)-activated intermediate-conductance IKCa1 channel when quiescent, and increase IKCa1 expression 45-fold upon activation with no change in Kv1.3 levels. In contrast, quiescent class-switched memory B cells express high levels of Kv1.3 ( approximately 2000 channels/cell) and maintain their Kv1.3(high) expression after activation. Consistent with their channel phenotypes, proliferation of naive and IgD(+)CD27(+) memory B cells is suppressed by the specific IKCa1 inhibitor TRAM-34 but not by the potent Kv1.3 blocker Stichodactyla helianthus toxin, whereas the proliferation of class-switched memory B cells is suppressed by Stichodactyla helianthus toxin but not TRAM-34. These changes parallel those reported for T cells. Therefore, specific Kv1.3 and IKCa1 inhibitors may have use in therapeutic manipulation of selective lymphocyte subsets in immunological disorders.
Wulff
Heike
H
Department of Medical Pharmacology and Toxicology, University of California, Davis, CA 95616, USA. hwuff@ucdavis.edu
Knaus
Hans-Günther
HG
Pennington
Michael
M
Chandy
K George
KG
D015551:Autoimmunity / Q000276:immunology* / Q000502:physiology; D001402:B-Lymphocytes / Q000276:immunology / Q000502:physiology*; D002454:Cell Differentiation / Q000276:immunology / Q000502:physiology*; D006801:Humans; D007072:Immunoglobulin D / Q000276:immunology / Q000502:physiology; D007156:Immunologic Memory / Q000276:immunology / Q000502:physiology; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; D051664:Kv1.3 Potassium Channel; D008221:Lymphoid Tissue / Q000276:immunology / Q000502:physiology; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000096:biosynthesis / Q000235:genetics*; D024642:Potassium Channels, Voltage-Gated; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000276:immunology / Q000502:physiology
D007072:Immunoglobulin D; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; C496973:KCNA3 protein, human; C496923:KCNN4 protein, human; D051664:Kv1.3 Potassium Channel; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7