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 Ca2+-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 (∼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.
|Original language||English (US)|
|Number of pages||11|
|Journal||Journal of Immunology|
|State||Published - Jul 15 2004|
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