Human B cell activation: Selective sensitivity of the early stages to calcium channel‐blocking drugs

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Abstract
The importance of Ca2+ in the early events of lymphocyte activation has been suggested by several studies. We examined the effect of calcium channel-blocking drugs (verapamil and nitrendipine) on the progression of human B cells through their activation cycle. Our results show that these drugs suppress the anti-μ-induced human B cell proliferation and interfere with the early events of the B cell activation in a dose-dependent fashion. This suppression correlates with a marked decrease in anti-μ-induced 45Ca2+ uptake. Calcium channel-blocking drugs inhibit the anti-μ-induced uridine incorporation and the appearance of the activation marker defined by the 4F2 monoclonal antibody. Calcium channel-blocking drugs also inhibit B cell proliferation induced by the costimulation with anti-μ antibody and B cell growth factor (BCGF). However, this inhibition takes place at the early (anti-μ-dependent) stage of B cell activation: the BCGF-dependent proliferation of in vitro anti-μ-activated B cells is only marginally inhibited. Finally the proliferation of Epstein-Barr virus-infected B cell lines is resistant to the effect of calcium channel-blocking drugs.