Critical role for mitochondria in B cell receptor-mediated apoptosis

Antigen-induced apoptosis of B cells serves to deplete the immune repertoire of anti-self specificities leading to central and peripheral B cell tolerance. However, the mechanism of B cell receptor (BCR)-mediated apoptosis is widely unknown. By using the human Burkitt lymphoma cell line BL60 as a mo...

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Bibliographic Details
Main Authors: Bouchon, Axel (Author) , Krammer, Peter H. (Author) , Walczak, Henning (Author)
Format: Article (Journal)
Language:English
Published: 30 August 2000
In: European journal of immunology
Year: 2000, Volume: 30, Issue: 1, Pages: 69-77
ISSN:1521-4141
DOI:https://doi.org/10.1002/1521-4141(200001)30:1<69::AID-IMMU69>3.0.CO;2-
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/https://doi.org/10.1002/1521-4141(200001)30:1<69::AID-IMMU69>3.0.CO;2-#
Verlag, lizenzpflichtig, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/1521-4141%28200001%2930%3A1%3C69%3A%3AAID-IMMU69%3E3.0.CO%3B2-%23
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Author Notes:Axel Bouchon, Peter H. Krammer and Henning Walczak
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Summary:Antigen-induced apoptosis of B cells serves to deplete the immune repertoire of anti-self specificities leading to central and peripheral B cell tolerance. However, the mechanism of B cell receptor (BCR)-mediated apoptosis is widely unknown. By using the human Burkitt lymphoma cell line BL60 as a model system for human germinal center B cells we show here that BCR-mediated apoptosis requires transcriptional activity but, in contrast to activation-induced T cell apoptosis, is neither mediated via known death receptor systems nor does it involve initial activation of caspase-8. Moreover, during BCR-induced apoptosis cytochrome c release and mitochondrial permeability transition (PT) precedecaspase activation. Although caspase inhibition after BCR stimulation blocks cleavage of caspase substrates and DNA fragmentation it does not prevent mitochondrial PT, cytochrome c release and cell death. Thus, BCR-mediated apoptosis is initiated by the caspase-independent induction of mitochondrial PT resulting in release of cytochrome c and subsequent activation of caspase-9, downstream caspases and apoptosis.
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Physical Description:Online Resource
ISSN:1521-4141
DOI:https://doi.org/10.1002/1521-4141(200001)30:1<69::AID-IMMU69>3.0.CO;2-