Extracellular but not intracellular calcium mobilization is required for Epstein-Barr virus-containing supernatant-induced B cell activation.
Changes in intracytosolic free calcium concentration ([Ca2+]i) are though to be an important trigger for the initiation of the cellular events culminating in B cell activation. After exposure of human B lymphocytes loaded with the fluorescent indicator quin-2 to the Epstein-Barr virus (EBV)-containing supernatant of B95-8 cell line, a rise in [Ca2+]i is observed. To determine the respective contribution of the intra- and extracellular Ca2+ pools in EBV-induced B cell activation, the pharmacologic modulation of these processes was investigated using an intracellular calcium chelator, 1,2-bis(o-aminophenoxy)ethane- N,N,N',N'-tetraacetic (BAPTA) or the calcium channel blocking drugs. When the extracellular Ca2+ contribution was minimized in the presence of calcium channel-blocking drugs or incubation of the cells in Ca2+-free medium, the EBV-induced human B cell activation was fully inhibited. When the calcium channel-blocking drugs, either verapamil or diltiazem, were withdrawn or when exogenous Ca2+ was added to the Ca2+-free medium, EBV-induced B cell activation was noted, demonstrating the reversibility of the inhibition. On the contrary, when the intracellular Ca2+ contribution was reduced after loading the cell with BAPTA, no alteration of the EBV-induced B cell activation was observed. Thus, the EBV-induced rise of [Ca2+]i required in the activation of human B cells appears to be essentially related to the entry of extracellular Ca2+ and not to the release of Ca2+ from internal stores.
Dugas
B
B
Institut Henri Beaufour, Les Ulis, France.
Mencia-Huerta
J M
JM
Braquet
P
P
Galanaud
P
P
Delfraissy
J F
JF
D001402:B-Lymphocytes / Q000276:immunology*; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology / Q000031:analogs & derivatives; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D008213:Lymphocyte Activation
D002121:Calcium Channel Blockers; D004533:Egtazic Acid; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium