Molecular mechanisms for apoptosis induced by signaling through the B cell antigen receptor.
Although the B cell antigen receptor (BCR) transmits survival and activation signals, BCR ligation can induce apoptosis in both immature and mature B cells. BCR-mediated apoptosis is suggested to play a role in self-tolerance by deleting self-reactive B cells. Generation of an apoptotic signal through BCR appears to depend on the composition of the higher order BCR complex and is suggested to occur outside the plasma membrane microdomains, termed lipid rafts. During BCR-mediated apoptosis, mitochondrial dysfunction is induced and is essential for apoptosis, probably by activating both caspases, cysteine proteases that play a central role in apoptosis, and caspase-independent effectors for apoptosis. Although signaling pathways for apoptosis are not yet fully defined in BCR-mediated apoptosis, expression of the proto-oncogene product c-Myc is enhanced upon BCR ligation, and c-Myc appears to mediate BCR ligation-induced apoptosis by causing mitochondrial dysfunction, suggesting that BCR-mediated apoptosis is a form of Myc-induced apoptosis.
Tsubata
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Department of Immunology, Medical Research Institute, Tokyo Medical and Dental University, Japan. tsubata.imm@mri.tmd.ac.jp
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000276:immunology / Q000378:metabolism; D018448:Models, Immunological; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D015398:Signal Transduction
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc; D011947:Receptors, Antigen, B-Cell; D020169:Caspases