Human B cell activation: selective sensitivity of the early stages to calcium channel-blocking drugs.
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.
B
B
Dugas
A
A
Vazquez
J F
JF
Delfraissy
J P
JP
Gérard
M T
MT
Rannou
P
P
Galanaud
D000941:Antigens / Q000032:analysis; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002460:Cell Line; D002472:Cell Transformation, Viral; D004305:Dose-Response Relationship, Drug; D006133:Growth Substances / Q000494:pharmacology; D004854:Herpesvirus 4, Human; D006801:Humans; D007148:Immunoglobulin mu-Chains / Q000276:immunology; D015847:Interleukin-4; D008213:Lymphocyte Activation / Q000187:drug effects*; D008222:Lymphokines / Q000494:pharmacology; D012313:RNA / Q000096:biosynthesis; D014268:Trifluoperazine / Q000494:pharmacology
D000941:Antigens; D002121:Calcium Channel Blockers; D006133:Growth Substances; D007148:Immunoglobulin mu-Chains; D008222:Lymphokines; D015847:Interleukin-4; D014268:Trifluoperazine; D012313:RNA; D002118:Calcium