Expression of TASK-2 and its upregulation by B cell receptor stimulation in WEHI-231 mouse immature B cells

Abstract

Stimulation of B cell receptors (BCR ligation) induces apoptosis of immature B cells, which is critical to the elimination of self-reactive clones. In the mouse immature B cell line WEHI-231, the authors previously reported two types of background K+ channels with large (~300 pS, LK(bg)) and medium (~100 pS, MK(bg)) conductance in divalent cation-free conditions. While the authors have recently identified LK(bg) as TREK-2, the molecular nature of MK(bg) is unknown yet. In the present study, the authors found that BCR ligation markedly increased the background K+ conductance of WEHI-231. A single-channel study revealed that MK(bg) activity is increased by BCR ligation and that the biophysical properties (unitary conductance and pH sensitivity) of MK(bg) are consistent with those of TWIK-related acid-sensitive K+ channel 2 (TASK-2). The expression of TASK-2 and its upregulation by BCR ligation were confirmed by RT-PCR and immunoblot assays in WEHI-231. The BCR ligation-induced increase of K+ current was prevented by calcineurin inhibitors (cyclosporine A or FK506), and also by TASK-2-specific small interfering RNA (siRNA) transfection (si-TASK-2). Furthermore, si-TASK-2 attenuated the apoptosis of WEHI-231 caused by BCR ligation. TASK-2 activity and its mRNA were also confirmed in the primary splenic B cells of mouse. Summarizing, the authors report for the first time the expression of TASK-2 in B cells and surmise that the upregulation of TASK-2 by BCR ligation is associated with the apoptosis of immature B cells.