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PMID:8313913
| Citation |
Merino, R, Ding, L, Veis, DJ, Korsmeyer, SJ and Nuñez, G (1994) Developmental regulation of the Bcl-2 protein and susceptibility to cell death in B lymphocytes. EMBO J. 13:683-91 |
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| Abstract |
Cell death is a prominent feature of B cell development. For example, a large population of B cells dies at the pre-B cell stage presumably due to the failure to express a functional immunoglobulin receptor. In addition, developing B cells expressing antigen receptors for self are selectively eliminated at the immature B cell stage. The molecular signals that control B cell survival are largely unknown. The product of the bcl-2 proto-oncogene may be involved as its overexpression inhibits apoptotic cell death in a variety of biological systems. However, the physiological role of the endogenous Bcl-2 protein during B cell development is undetermined. Here we show a striking developmental regulation of the Bcl-2 protein in B lymphocytes. Bcl-2 is highly expressed in CD43+ B cell precursors (pro-B cells) and mature B cells but downregulated at the pre-B and immature B cell stages of development. We found that Bcl-2 expressed by B cells is a long-lived protein with a half-life of approximately 10 h. Importantly, susceptibility to apoptosis mediated by the glucocorticoid hormone dexamethasone is stage-dependent in developing B cells and correlates with the levels of Bcl-2 protein. Furthermore, expression of a bcl-2 transgene rescued pre-B and immature B cells from dexamethasone-induced cell death, indicating that Bcl-2 can inhibit the apoptotic cell death of progenitors and early B cells. Taken together, these findings argue that Bcl-2 is a physiological signal controlling cell death during B cell development. |
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| Keywords |
Animals; Antibodies, Monoclonal; B-Lymphocytes/cytology; Base Sequence; Blotting, Western; Cell Death; Cell Differentiation; DNA; Dexamethasone/pharmacology; Down-Regulation; Mice; Mice, Inbred C57BL; Mice, Transgenic; Molecular Sequence Data; Proto-Oncogene Proteins/metabolism; Proto-Oncogene Proteins c-bcl-2; Stem Cells/metabolism |
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Significance
Annotations
| Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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