| Abstract | Antigen binding to the B-cell receptor (BCR) of pre-mature B lymphocytes induces their apoptotic cell death, but binding to the BCR of mature B lymphocytes triggers activation and proliferation. Binding to pre-mature B lymphocytes is thought not only to function as a mechanism to exclude B-cell clones that possess the ability to react with self-antigen, but also to act as a defense mechanism in auto-immune diseases. Cross-linking of BCR of pre-mature B-cell lines, including the chicken DT40 cell line, with anti-immunoglobulin IgG induces apoptotic cell death. Treatment with phorbol 12-myristate 13-acetate/ionomycin, which mimics BCR stimulation, is used to study intracellular signal transduction of B lymphocytes. Here, by analyzing the E2A-deficient DT40 cell line, E2A(-/-), we show that E2A deficiency prevents certain levels of apoptotic cell death mediated by BCR signaling. In addition, E2A deficiency-linked BCR signaling controls the mimicked pre-mature B-cell apoptosis by PMA/ionomycin through elevated survivin plus inhibitor of apoptosis 2 levels, and reduced caspase-3 and caspase-8 activities, resulting in increased amounts of ICAD (inhibitor of caspase-activated DNase), compared with those in the presence of E2A, followed by reduction of DNA fragmentation. These findings will contribute to the resolution of molecular mechanisms of negative selection of B cells and also auto-immune diseases. |
| Authors | Kenji Toyonaga, Hidehiko Kikuchi, Koki Yamashita, Masami Nakayama, Kazuo Chijiiwa, Tatsuo Nakayama
(Affiliation: Department of Medical Sciences, Miyazaki Medical College, University of Miyazaki, Miyazaki, Japan.)
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| Journal | The FEBS journal
(FEBS J)
Vol. 276
Issue 5
Pg. 1418-28
(Mar 2009)
ISSN: 1742-4658 [Electronic] England |
| PMID | 19187225
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
| Chemical References |
- Basic Helix-Loop-Helix Transcription Factors
- Inhibitor of Apoptosis Proteins
- Microtubule-Associated Proteins
- Receptors, Antigen, B-Cell
- Ionomycin
- Caspase 8
|
| Topics |
- Animals
- Apoptosis
(immunology)
- Basic Helix-Loop-Helix Transcription Factors
(metabolism)
- Caspase 8
(genetics, metabolism)
- Cell Survival
- Cells, Cultured
- Chickens
- Inhibitor of Apoptosis Proteins
(genetics, metabolism)
- Ionomycin
(pharmacology)
- Microtubule-Associated Proteins
(metabolism)
- Precursor Cells, B-Lymphoid
(immunology)
- Receptors, Antigen, B-Cell
(immunology, metabolism)
- Signal Transduction
(immunology)
- Transcription, Genetic
|
