| Abstract | The 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. |
| Authors | Hidehiko Kikuchi, Tatsuo Nakayama
(Affiliation: Department of Life Science, Frontier Science Research Center, University of Miyazaki, Kiyotake, Miyazaki, Japan.)
|
| Journal | Gene
(Gene)
Vol. 419
Issue 1-2
Pg. 48-55
(Aug 1 2008)
ISSN: 0378-1119 Netherlands |
| PMID | 18538956
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
| Chemical References |
- Apoptosis Regulatory Proteins
- Inhibitor of Apoptosis Proteins
- NF-kappa B
- Receptors, Antigen, B-Cell
- caspase-activated DNase inhibitor
- Tetradecanoylphorbol Acetate
- Ionomycin
- p300-CBP Transcription Factors
- p300-CBP-associated factor
- Protein Kinase C
- Caspases
|
| Topics |
- Animals
- Apoptosis
- Apoptosis Regulatory Proteins
(genetics, metabolism)
- Caspases
(metabolism)
- Cell Line
- Cell Survival
- Chickens
(immunology)
- Enzyme Activation
- Gene Deletion
- Gene Expression Regulation
- Inhibitor of Apoptosis Proteins
(genetics, metabolism)
- Ionomycin
(pharmacology)
- NF-kappa B
(metabolism)
- Precursor Cells, B-Lymphoid
(drug effects, immunology)
- Protein Kinase C
(genetics, metabolism)
- Receptors, Antigen, B-Cell
(drug effects, metabolism)
- Signal Transduction
- Tetradecanoylphorbol Acetate
(pharmacology)
- p300-CBP Transcription Factors
(genetics, metabolism)
|
