Abstract:
:During the germinal centre reaction (GC), B cells with non-functional or self-reactive antigen receptors are negatively selected by apoptosis to generate B cell repertoire with appropriate antigen specificities. We studied the molecular mechanism of Fas/CD95- and B cell receptor (BCR)-induced apoptosis to shed light on the signalling events involved in the negative selection of GC B cells. As an experimental model, we used human follicular lymphoma (FL) cell line HF1A3, which originates from a GC B cell, and transfected HF1A3 cell lines overexpressing Bcl-x(L), c-FLIP(long) or dominant negative (DN) caspase-9. Fas-induced apoptosis was dependent on the caspase-8 activation, since the overexpression of c-FLIP(long), a natural inhibitor of caspase-8 activation, blocked apoptosis induced by Fas. In contrast, caspase-9 activation was not involved in Fas-induced apoptosis. BCR-induced apoptosis showed the typical characteristics of mitochondria-dependent (intrinsic) apoptosis. Firstly, the activation of caspase-9 was involved in BCR-induced DNA fragmentation, while caspase-8 showed only marginal role. Secondly, overexpression of Bcl-x(L) could block all apoptotic changes induced by BCR. As a novel finding, we demonstrate that caspase-9 can enhance the cytochrome-c release and collapse of mitochondrial membrane potential (DeltaPsi(m)) during BCR-induced apoptosis. The requirement of different signalling pathways in apoptosis induced by BCR and Fas may be relevant, since Fas- and BCR-induced apoptosis can thus be regulated independently, and targeted to different subsets of GC B cells.
journal_name
Scand J Immunoljournal_title
Scandinavian journal of immunologyauthors
Eeva J,Nuutinen U,Ropponen A,Mättö M,Eray M,Pellinen R,Wahlfors J,Pelkonen Jdoi
10.1111/j.1365-3083.2009.02331.xsubject
Has Abstractpub_date
2009-12-01 00:00:00pages
574-83issue
6eissn
0300-9475issn
1365-3083pii
SJI2331journal_volume
70pub_type
杂志文章abstract::Peripheral blood mononuclear leucocytes (PBLs) stimulated in vitro by heat-killed formaldehyde-fixed Staphylococcus aureus Cowan I (SACoI) produced acid-labile alpha interferon (IFN-alpha) and, to various extents, also IFN-gamma. The IFN producers resided in nylon wool-nonadherent cells, and monocytes suppressed SACoI...
journal_title:Scandinavian journal of immunology
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journal_title:Scandinavian journal of immunology
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journal_title:Scandinavian journal of immunology
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journal_title:Scandinavian journal of immunology
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journal_title:Scandinavian journal of immunology
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journal_title:Scandinavian journal of immunology
pub_type: 杂志文章
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journal_title:Scandinavian journal of immunology
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journal_title:Scandinavian journal of immunology
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journal_title:Scandinavian journal of immunology
pub_type: 杂志文章
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pub_type: 杂志文章
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更新日期:2007-01-01 00:00:00
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journal_title:Scandinavian journal of immunology
pub_type: 杂志文章
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更新日期:1991-12-01 00:00:00
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journal_title:Scandinavian journal of immunology
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pub_type: 杂志文章
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更新日期:1975-01-01 00:00:00
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journal_title:Scandinavian journal of immunology
pub_type: 杂志文章
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journal_title:Scandinavian journal of immunology
pub_type: 杂志文章
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更新日期:2003-03-01 00:00:00
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journal_title:Scandinavian journal of immunology
pub_type: 杂志文章
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更新日期:1993-06-01 00:00:00
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pub_type: 杂志文章
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更新日期:2007-04-01 00:00:00