title: ERK1/2 has an essential role in B cell receptor- and CD40-induced signaling in an in vitro model of germinal center B cell selection.
abstract: Germinal center (GC) B cells undergo apoptosis after B cell receptor (BCR) ligation, unless they receive CD40-mediated survival signal from helper T cells. In the present study, we used a human follicular lymphoma cell line HF1A3, as an in vitro model to study the selection process in germinal centers. We show here that BCR ligation led to immediate ERK1/2 activation and phosphorylations of its downstream targets, Bim EL/L and Bcl-2 (at Ser70) which resulted in short-term survival. On the other hand, during the late phase of BCR signaling, ERK1/2 phosphorylation was inhibited which resulted in apoptosis. In addition, CD40 signaling led to sustained ERK1/2 activation and up-regulation of Bcl-xL in BCR-primed HF1A3 GC B cells. In conclusion, MEK-ERK pathway and Bcl-2 family proteins are crucial players in BCR-mediated survival/apoptosis and CD40-mediated survival.
authors.affiliation: Department of Clinical Microbiology, Institute of Clinical Medicine, University of Eastern Finland, Yliopistonranta 1 C, 70210 Kuopio, Finland; Cancer Center of University of Eastern, Kuopio, Finland. Electronic address: jemal.adem@uef.fi.
authors.forename: Jemal
authors.initials: J
authors.lastname: Adem
authors.affiliation: Department of Clinical Microbiology, Institute of Clinical Medicine, University of Eastern Finland, Yliopistonranta 1 C, 70210 Kuopio, Finland.
authors.forename: Aleksi
authors.initials: A
authors.lastname: Hämäläinen
authors.affiliation: Department of Clinical Microbiology, Institute of Clinical Medicine, University of Eastern Finland, Yliopistonranta 1 C, 70210 Kuopio, Finland.
authors.forename: Antti
authors.initials: A
authors.lastname: Ropponen
authors.affiliation: Department of Clinical Microbiology, Institute of Clinical Medicine, University of Eastern Finland, Yliopistonranta 1 C, 70210 Kuopio, Finland.
authors.forename: Jonna
authors.initials: J
authors.lastname: Eeva
authors.affiliation: Fimlab LaboratoriesOy, Tampere University Hospital, PL66, 33101 Tampere, Finland; Department of Medicine, University of Tampere, Kalevantie 4, 33014 Tampere, Finland.
authors.forename: Mine
authors.initials: M
authors.lastname: Eray
authors.affiliation: Department of Clinical Microbiology, Institute of Clinical Medicine, University of Eastern Finland, Yliopistonranta 1 C, 70210 Kuopio, Finland.
authors.forename: Ulla
authors.initials: U
authors.lastname: Nuutinen
authors.affiliation: Department of Clinical Microbiology, Institute of Clinical Medicine, University of Eastern Finland, Yliopistonranta 1 C, 70210 Kuopio, Finland; Eastern Finland Laboratory Centre (ISLAB), Puijonlaaksontie 2, 70210 Kuopio, Finland; Cancer Center of University of Eastern, Kuopio, Finland.
authors.forename: Jukka
authors.initials: J
authors.lastname: Pelkonen
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001402:B-Lymphocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D000072224:Bcl-2-Like Protein 11; D002070:Butadienes / Q000494:pharmacology; D019013:CD40 Antigens / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D019610:Cytoprotection / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D018858:Germinal Center / Q000166:cytology*; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D008954:Models, Biological; D009570:Nitriles / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D051020:bcl-X Protein / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; C000606775:BCL2L11 protein, human; D000072224:Bcl-2-Like Protein 11; D002070:Butadienes; D019013:CD40 Antigens; D008565:Membrane Proteins; D009570:Nitriles; D011518:Proto-Oncogene Proteins; D011947:Receptors, Antigen, B-Cell; C113580:U 0126; D051020:bcl-X Protein; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
keywords: BCR; Bcl-2 family proteins; CD40; ERK1/2; Germinal center