Critical role for mitochondria in B cell receptor-mediated apoptosis

✍ Scribed by Axel Bouchon; Peter H. Krammer; Henning Walczak

• Publisher: John Wiley and Sons
• Year: 2000
• Tongue: English
• Weight: 167 KB
• Volume: 30
• Category: Article
• ISSN: 0014-2980
• DOI: 10.1002/1521-4141(200001)30:1<69::aid-immu69>3.0.co;2-#

✦ Synopsis

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 activationinduced 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) precede caspase 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.