N Sakata1, H Kawasome, N Terada, G L Johnson, E W Gelfand. 1. Division of Basic Sciences, Department of Pediatrics, Program in Molecular Signal Transduction, National Jewish Medical and Research Center, Denver, CO, USA.
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-1beta-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-1beta-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.
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-1beta-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-1beta-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.
Authors: Ali I Kuraishy; Samuel W French; Mara Sherman; Marco Herling; Dan Jones; Randolph Wall; Michael A Teitell Journal: Proc Natl Acad Sci U S A Date: 2007-06-04 Impact factor: 11.205