title: ER stress is involved in B cell antigen receptor ligation-induced apoptosis.
abstract: Apoptosis of B cells upon ligation of the B cell antigen receptor (BCR) plays a role in elimination of self-reactive B cells. Previously, BCR ligation was shown to induce expression of the molecules involved in the unfolded protein response (UPR). However, the role of the UPR in BCR-mediated apoptosis is poorly understood. Here, we demonstrate that activation of various UPR molecules are induced when BCR ligation induces apoptosis in the B cell line WEHI-231 and mouse spleen B cells. BCR ligation-induced UPR is attenuated by survival signaling through CD40 in these cells. When overexpression of BiP suppresses the UPR in WEHI-231 cells, activation of p38 MAPK is blocked and apoptosis is reduced. Moreover, the p38 MAPK inhibitor SB203580 reduces BCR ligation-induced apoptosis. These results suggest that the UPR is involved in BCR ligation-induced apoptosis and that p38 MAPK is crucial for apoptosis during the UPR in B cells.
authors.affiliation: Laboratory of Immunology, School of Biomedical Science, Tokyo Medical and Dental University, 1-5-45 Bunkyo-ku, Yushima, Tokyo 113-8510, Japan.
authors.forename: Bin-Cheng
authors.initials: BC
authors.lastname: Yan
authors.forename: Takahiro
authors.initials: T
authors.lastname: Adachi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tsubata
mesh_terms: D000818:Animals; D017209:Apoptosis; D001402:B-Lymphocytes / Q000276:immunology*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D051379:Mice; D017510:Protein Folding; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D011947:Receptors, Antigen, B-Cell; D048051:p38 Mitogen-Activated Protein Kinases