Antigen receptor-mediated signaling pathways in transitional immature B cells.
Engagement of antigen receptors on immature B cells induces apoptosis, while at the mature stage, it stimulates cell activation and proliferation. The difference in B cell receptor (BCR)-mediated signaling pathways regulating death or survival of B cells is not fully understood. We aimed to characterize the pathway leading to BCR-driven apoptosis. Transitional immature B cells were obtained from the spleen of sublethally irradiated and auto-reconstituted mice. We have detected a short-lived BCR-driven activation of mitogen-activated protein kinases (ERK1/2 and p38 MAPK) and Akt/PKB in transitional immature B cells that correlated with the lack of c-Fos expression, reduced phosphorylation of Akt substrates and a susceptibility for apoptosis. Simultaneous signaling through BCR and CD40 protected immature B cells from apoptosis, however, without inducing Bcl-2 expression. The BCR-induced apoptosis of immature B cells is a result of the collapse of mitochondrial membrane potential and the subsequent activation of caspase-3.
Kövesdi
Dorottya
D
Department of Immunology, Eötvös Loránd University, Pázmány Péter sétány 1/c, H-1117, Budapest, Hungary.
Pászty
Katalin
K
Enyedi
Agnes
A
Kiss
Endre
E
Matkó
János
J
Ludányi
Katalin
K
Rajnavölgyi
Eva
E
Sármay
Gabriella
G
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D019013:CD40 Antigens / Q000378:metabolism; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D016762:Genes, fos / Q000502:physiology; D008213:Lymphocyte Activation / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000502:physiology; D051379:Mice; D008928:Mitochondria / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D019013:CD40 Antigens; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011947:Receptors, Antigen, B-Cell; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases