dc.date.accessioned | 2018-06-12T09:09:13Z | |
dc.date.available | 2018-06-12T09:09:13Z | |
dc.date.created | 2018-01-24T10:30:35Z | |
dc.date.issued | 2017 | |
dc.identifier.citation | Bollum, Lise Kristin Huse, Kanutte Oksvold, Morten Pedersen Bai, Baoyan Hilden, Vera Irene Forfang, Lise Yoon, So Wälchli, Sébastien Smeland, Erlend B Myklebust, June . BMP-7 induces apoptosis in human germinal center B cells and is influenced by TGF-β receptor type I ALK5. PLoS ONE. 2017, 12(5) | |
dc.identifier.uri | http://hdl.handle.net/10852/61852 | |
dc.description.abstract | Selection and maturation of B cells into plasma cells producing high-affinity antibodies occur in germinal centers (GC). GCs form transiently in secondary lymphoid organs upon antigen challenge, and the GC reaction is a highly regulated process. TGF-β is a potent negative regulator, but the influence of other family members including bone morphogenetic proteins (BMPs) is less known. Studies of human peripheral blood B lymphocytes showed that BMP-6 suppressed plasmablast differentiation, whereas BMP-7 induced apoptosis. Here, we show that human naïve and GC B cells had a strikingly different receptor expression pattern. GC B cells expressed high levels of BMP type I receptor but low levels of type II receptors, whereas naïve B cells had the opposite pattern. Furthermore, GC B cells had elevated levels of downstream signaling components SMAD1 and SMAD5, but reduced levels of the inhibitory SMAD7. Functional assays of GC B cells revealed that BMP-7 suppressed the viability-promoting effect of CD40L and IL-21, but had no effect on CD40L- and IL-21-induced differentiation into plasmablasts. BMP-7-induced apoptosis was counteracted by a selective TGF-β type I receptor (ALK4/5/7) inhibitor, but not by a selective BMP receptor type I inhibitor. Furthermore, overexpression of truncated ALK5 in a B-cell line counteracted BMP-7-induced apoptosis, whereas overexpression of truncated ALK4 had no effect. BMP-7 mRNA and protein was readily detected in tonsillar B cells, indicating a physiological relevance of the study. Altogether, we identified BMP-7 as a negative regulator of GC B-cell survival. The effect was counteracted by truncated ALK5, suggesting greater complexity in regulating BMP-7 signaling than previously believed. | en_US |
dc.language | EN | |
dc.publisher | Public Library of Science (PLoS) | |
dc.rights | Attribution 4.0 International | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | |
dc.title | BMP-7 induces apoptosis in human germinal center B cells and is influenced by TGF-β receptor type I ALK5 | en_US |
dc.type | Journal article | en_US |
dc.creator.author | Bollum, Lise Kristin | |
dc.creator.author | Huse, Kanutte | |
dc.creator.author | Oksvold, Morten Pedersen | |
dc.creator.author | Bai, Baoyan | |
dc.creator.author | Hilden, Vera Irene | |
dc.creator.author | Forfang, Lise | |
dc.creator.author | Yoon, So | |
dc.creator.author | Wälchli, Sébastien | |
dc.creator.author | Smeland, Erlend B | |
dc.creator.author | Myklebust, June | |
cristin.unitcode | 185,53,49,0 | |
cristin.unitname | Kreftklinikken | |
cristin.ispublished | true | |
cristin.fulltext | original | |
cristin.qualitycode | 1 | |
dc.identifier.cristin | 1550611 | |
dc.identifier.bibliographiccitation | info:ofi/fmt:kev:mtx:ctx&ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=PLoS ONE&rft.volume=12&rft.spage=&rft.date=2017 | |
dc.identifier.jtitle | PLoS ONE | |
dc.identifier.volume | 12 | |
dc.identifier.issue | 5 | |
dc.identifier.doi | http://dx.doi.org/10.1371/journal.pone.0177188 | |
dc.identifier.urn | URN:NBN:no-64452 | |
dc.type.document | Tidsskriftartikkel | en_US |
dc.type.peerreviewed | Peer reviewed | |
dc.source.issn | 1932-6203 | |
dc.identifier.fulltext | Fulltext https://www.duo.uio.no/bitstream/handle/10852/61852/2/BMP-7%2Binduces%2Bapoptosis%2Bin%2Bhuman%2Bgerminal%2Bcenter%2BB%2Bcells%2Band%2Bis%2Binfluenced%2Bby%2BTGF-B%2Breceptor%2Btype%2BI%2BALK5_PLosOne.pdf | |
dc.type.version | PublishedVersion | |
dc.relation.project | NFR/179571 | |
dc.relation.project | HSØ/27044 | |
dc.relation.project | KF/33549 | |