K super(+) 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 super(+)CD27 super(+) memory B cells express small numbers of the voltage-gated Kv1.3 an...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2004-07, Vol.173 (2), p.776-786
Main Authors: Wulff, Heike, Knaus, Hans-Guenther, Pennington, Michael, Chandy, KGeorge
Format: Article
Language:English
Subjects:
Stichodactyla helianthus
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Summary: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 super(+)CD27 super(+) memory B cells express small numbers of the voltage-gated Kv1.3 and the Ca super(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 ([approx]2000 channels/cell) and maintain their Kv1.3 super(high) expression after activation. Consistent with their channel phenotypes, proliferation of naive and IgD super(+)CD27 super(+) 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.
ISSN:0022-1767