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

Dugas, Bernard; Mencia‐Huerta, Jean‐Michel; Braquet, P.; Galanaud, Pierre; Delfraissy, Jean‐François

doi:10.1002/eji.1830191017

Cited by 6 publications

(3 citation statements)

References 35 publications

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“…Effect gized in the presence of the B subunit of CT.stimulates only the entry of Ca2+ into the cell.This increase appears to be long lasting, as has recently been shown for EBV stimulation of B lymphocytes[17]. Also, as for EBV-induced B lymphocyte activation, the B subunit did not induce neither [Ca2+]i changes nor the proliferation of the cells in the absence of extracellular Ca2+…”

supporting

confidence: 67%

Effect of bacterial toxins on human B cell activation. II. Mitogenic activity of the B subunit of cholera toxin

Dugas¹,

Paul‐Eugène²,

Génot

et al. 1991

Eur J Immunol

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The B subunit of cholera toxin (CT) but not the entire CT was found to induce the proliferation of resting human B lymphocytes. A significant mitogenic effect was observed for B subunit concentrations greater than 1 microgram/ml and reached a maximum of stimulation at 10 micrograms/ml. As already described for B lymphocytes preactivated with Staphylococcus aureus Cowan Strain I (SAC). B lymphocytes preactivated with the B subunit of CT, but not with the entire CT, were able to proliferate in response to exogenous interleukin 2 (IL 2) and to the low-molecular weight B cell growth factor (BCGF). To determine the transmembrane signaling system used by the B subunit of CT to mediate its biological effects, we compared the transmembrane signals used by the entire CT, its B subunit and SAC. In comparison to the entire CT, which directly activates adenylate cyclase and increases intracellular cAMP levels, neither the B subunit nor SAC modified the cAMP content. In contrast, although SAC induced inositol phosphate generation neither CT nor the separate subunits were able to induce such a production. Moreover, changes in the fluorescence of indo-1-loaded B lymphocytes revealed that mitogenic doses of either the B subunit or SAC induced a rapid and sustained increase in cytoplasmic free Ca2+ concentration ([Ca2+]i). The effect of the B subunit appeared to be largely dependent on the presence of extracellular Ca2+, because in Ca2(+)-free medium no [Ca2+]i uptake was observed. In contrast, the SAC-induced [Ca2+]i uptake is substantially, but not totally, inhibited in Ca2(+)-free medium, suggesting that part of the rise in [Ca2+]i was due to the release from internal stores. Moreover, fluorimetric measurements on loaded cells with 2',7'-bis(carboxyethyl)-5(6')-carboxyfluorescein revealed that SAC induced a rapid cytoplasmic alkalinization via activation of Na+/H+ exchange, whereas the entire CT and its B subunit had no effect on intracellular pH. Taken together, these data suggest that, in comparison to SAC, the mitogenic effect of the B subunit of CT was mediated through different intracellular biochemical pathways.

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confidence: 67%

Effect of bacterial toxins on human B cell activation. II. Mitogenic activity of the B subunit of cholera toxin

Dugas¹,

Paul‐Eugène²,

Génot

et al. 1991

Eur J Immunol

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“…For studies with the calpain inhibitor PD150606, APCs were cultured in Ca 2 ϩ -free media. B-LCLs typically display a high Ca 2 ϩ influx because of the expression of the EBV-encoded latent membrane protein 1 (24). In some experiments, Priess-GAD cells were acid washed before incubation with inhibitors.…”

Section: Methodsmentioning

confidence: 99%

Cytoplasmic Processing Is a Prerequisite for Presentation of an Endogenous Antigen by Major Histocompatibility Complex Class II Proteins

Lich

Elliott

Blum

2000

The Journal of Experimental Medicine

131

115

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Biochemical and functional studies have demonstrated major histocompatibility complex (MHC) class II–restricted presentation of select epitopes derived from cytoplasmic antigens, with few insights into the processing reactions necessary for this alternate pathway. Efficient presentation of an immunodominant epitope derived from glutamate decarboxylase (GAD) was observed regardless of whether this antigen was delivered exogenously or via a cytoplasmic route into human histocompatibility leukocyte antigen class II–DR4+ antigen-presenting cells. Presentation of exogenous as well as cytoplasmic GAD required the intersection of GAD peptides and newly synthesized class II proteins. By contrast, proteolytic processing of this antigen was highly dependent upon the route of antigen delivery. Exogenous GAD followed the classical pathway for antigen processing, with an absolute requirement for endosomal/lysosomal acidification as well as cysteine and aspartyl proteases resident within these organelles. Presentation of endogenous GAD was dependent upon the action of cytoplasmic proteases, including the proteasome and calpain. Thus, translocation of processed antigen from the cytoplasm into membrane organelles is necessary for class II–restricted presentation via this alternate pathway. Further trimming of these peptides after translocation was mediated by acidic proteases within endosomes/lysosomes, possibly after or before class II antigen binding. These studies suggest that processing of exogenous and cytoplasmic proteins occurs through divergent but overlapping pathways. Furthermore, two cytoplasmic proteases, the proteasome and calpain, appear to play important roles in MHC class II–restricted antigen presentation.

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“…Epstein-Barr virus (EBV, or HHV-4), a member of the Herpesviridae family, large DNA viruses with an enveloped virion, is the etiological agent of infectious mononucleosis and a number of malignancies, such as Burkitt's lymphoma and nasopharyngeal carcinoma. In B lymphocytes, EBV infection can induce a rise in [Ca 2+ ] CYT due to increased Ca 2+ influx from the extracellular space [49]. The rise in intracellular Ca 2+ can be blocked by verapamil, a L-type Ca 2+ -channel blocker [50].…”

Section: Voc and Rocmentioning

confidence: 99%

Viral calciomics: Interplays between Ca2+ and virus

2009

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Ca2+ is one of the most universal and versatile signaling molecules and is involved in almost every aspect of cellular processes. Viruses are adept at utilizing the universal Ca2+ signal to create a tailored cellular environment that meets their own demands. This review summarizes most of the known mechanisms by which viruses perturb Ca2+ homeostasis and utilize Ca2+ and cellular Ca2+-binding proteins to their benefit in their replication cycles. Ca2+ plays important roles in virion structure formation, virus entry, viral gene expression, posttranslational processing of viral proteins and virion maturation and release. As part of the review, we introduce an algorithm to identify linear “EF-hand” Ca2+-binding motifs which resulted in the prediction of a total of 93 previously unrecognized Ca2+-binding motifs in virus proteins. Many of these proteins are nonstructural proteins, a class of proteins among which Ca2+ interactions had not been formerly appreciated. The presence of linear Ca2+-binding motifs in viral proteins enlarges the spectrum of Ca2+–virus interplay and expands the total scenario of viral calciomics.

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

Cited by 6 publications

References 35 publications

Effect of bacterial toxins on human B cell activation. II. Mitogenic activity of the B subunit of cholera toxin

Effect of bacterial toxins on human B cell activation. II. Mitogenic activity of the B subunit of cholera toxin

Cytoplasmic Processing Is a Prerequisite for Presentation of an Endogenous Antigen by Major Histocompatibility Complex Class II Proteins

Viral calciomics: Interplays between Ca2+ and virus

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