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 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.