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

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-mu-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-mu-induced 45Ca2+ uptake. Calcium channel-blocking drugs inhibit the anti-mu-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-mu antibody and B cell growth factor (BCGF). However, this inhibition takes place at the early (anti-mu-dependent) stage of B cell activation: the BCGF-dependent proliferation of in vitro anti-mu-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.

Extracellular but not intracellular calcium mobilization is required for epstein‐barr virus‐containing supernatant‐induced b cell activation

“…However, since EBV-containing SN and not purified virus were used, the possibility that the initial rise in [Ca2+]i could be due to another component than the viral particle itself cannot be ruled out. This possibility is supported by the fact that an anti-CD21 mAb only partially blocks the early increase in [Ca2+]i induced by the addition of EBV-containing SN [28]. It should be stressed that under our experimental conditions the anti-CD21 mAb had no effect by itself on B cell activation (data not shown and P81) * quin-2, as indicated by two lines of evidences: (a) the [Ca2+], increase related to an influx of extracellular Ca2+ is not transient but sustained (always observable after 30 min) and (b) similar results were obtained using indo-1 (data not shown), which presented a lower buffering capacity than quin-2 [36].…”

“…Correspondence: Bernard [28]. In the present work, the respective contribution of the extra-and intracellular pools of Ca2+ in the increase in [Ca2+]i was studied.…”

Non-voltage-gated L-type Ca2+ Channels in Human T Cells

“…Initial evidence for the presence of L-type Ca 2ϩ channels in lymphocytes relied on pharmacological studies using antagonists of these channels. A number of studies showed effects of these antagonists on B and T cell activation (21)(22)(23)(24). However, the drugs were used at higher concentrations than those used to block authentic voltage-gated Ca 2ϩ channels.…”

Herpes simplex virus-1-specific proteins are involved in alteration of polyphosphoinositide metabolism in baby-hamster kidney cells

“…Phosphoinositides are well known as substrates for phospholipase C, and thus as precursors of the second messengers inositol trisphosphate and diacylglycerol (reviewed by Berridge, 1985). It was recently reported that the herpes virus Epstein-Barr virus induces protein kinase C activation, probably through phospholipase C activation (Dugas et al, 1988). The human immunodeficiency virus (HIV)-1 glycoprotein gp120 can induce increased levels of inositol trisphosphate in CD4-positive lymphocytes (Kornfeld et al, 1988).…”