Hidehiko Kikuchi, Tatsuo Nakayama
Department of Life Science, Frontier Science Research Center, University of Miyazaki, Kiyotake, Miyazaki, Japan.
Gene 2008 Aug 1The antigen binding to the B cell receptor (BCR) of pre-mature B lymphocytes induces their apoptotic cell death, although the binding to BCR of mature B lymphocytes does their activation and proliferation. The former is thought not only to function as a mechanism to exclude B cell clones possessing the ability to react with self-antigen, but also to participate as a defense mechanism from auto-immune diseases. Cross-linking of BCR of pre-mature B cell lines, including the chicken DT40 cell line, with anti-immunoglobulin antibody induces their apoptotic cell death. The PMA/ionomycin treatment, which mimics the BCR stimulation, is used to study intracellular signal transduction of B lymphocytes. Here, by analyzing the GCN5-deficient DT40 cell line, we show that GCN5 and BCR signalling are essential for apoptotic cell death. In addition, GCN5 and BCR signalling control cooperatively pre-mature B cell apoptosis via both depletions of ICAD and IAP2 (inhibitors for apoptosis) and elevations of caspase-8 and caspase-3 activities, resulting in increased activity of CAD (effector for apoptosis) followed by the DNA fragmentation. These findings should be useful in understanding the molecular mechanisms involved in negative selection of B cells as also in auto-immune diseases.
Hidehiko Kikuchi, Tatsuo Nakayama. GCN5 and BCR signalling collaborate to induce pre-mature B cell apoptosis through depletion of ICAD and IAP2 and activation of caspase activities. Gene. 2008 Aug 1;419(1-2):48-55
PMID: 18538956
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