CD40 and adenosine A2 receptor agonist–cyclic adenosine monophosphate rescue B-cell antigen receptor–induced apoptosis through independent pathways and converge to prevent caspase activation - 04/09/11
Abstract |
Background: Antigen receptor ligation induces apoptosis of B lymphocytes, but the molecular mechanisms underlying induction of apoptosis remain unclear, although the growing family of IL-1β–converting enzyme cysteine proteases (caspases) are recognized to be major effectors of cellular death. Objective: We sought to delineate and compare the rescue of B-cell apoptosis through CD40 ligand-CD40 interaction and cyclic adenosine monophosphate (cAMP)–dependent protein kinase A in human B cells. Methods: By using tonsillar B cells and the B-lymphoblastoid cell line Ramos, rescue from B-cell apoptosis was compared, as were signaling pathways after activation of cells through CD40 and the adenosine A2 receptor. Results: Both CD40 ligand-CD40 interaction and activation of intracellular cAMP rescue B cells from apoptosis after antigen receptor ligation. Although these pathways do not overlap, they converge by preventing the anti-IgM–induced activation of CPP32 (caspase 3), a member of the IL-1β–converting enzyme protease family. Conclusion: These data indicate that the cAMP-protein kinase A–dependent and CD40-signaling pathways regulate B-cell survival and converge at a common point, the inhibition of antigen receptor–induced activation of caspases. (J Allergy Clin Immunol 2000;105:522-31.)
Il testo completo di questo articolo è disponibile in PDF.Keywords : B cells, apoptosis, cyclic adenosine monophosphate, CD40
Abbreviations : ATP:, cAMP:, dbcAMP:, DMSO:, ERK:, JNK:, MBP:, MEK:, PKA:
Mappa
Supported in part by Grants AI HL-36577 (to E.W.G.) and DK-37871 (to G.L.J.) from the National Institutes of Health. |
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Reprint requests: Erwin W. Gelfand, MD, 1400 Jackson St, Denver, CO 80206. |
Vol 105 - N° 3
P. 522-531 - Marzo 2000 Ritorno al numeroBenvenuto su EM|consulte, il riferimento dei professionisti della salute.
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