TY - JOUR
T1 - K+ channel expression during B cell differentiation
T2 - Implications for immunomodulation and autoimmunity
AU - Wulff, Heike
AU - Knaus, Hans Günther
AU - Pennington, Michael
AU - Chandy, K. George
PY - 2004/7/15
Y1 - 2004/7/15
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=3142775617&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=3142775617&partnerID=8YFLogxK
M3 - Article
C2 - 15240664
AN - SCOPUS:3142775617
VL - 173
SP - 776
EP - 786
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 2
ER -