Developmental regulation of the Bcl-2 protein and susceptibility to cell death in B lymphocytes

Ramón Merino, Liyun Ding, Deborah J. Veis, Stanley J. Korsmeyer, Gabriel Nuñez

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276 Scopus citations

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 protooncogene 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 ~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.

Original languageEnglish
Pages (from-to)683-691
Number of pages9
JournalEMBO Journal
Volume13
Issue number3
StatePublished - Feb 1 1994

Keywords

  • Apoptosis
  • B cell development
  • Bcl-2
  • Cell death

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    Merino, R., Ding, L., Veis, D. J., Korsmeyer, S. J., & Nuñez, G. (1994). Developmental regulation of the Bcl-2 protein and susceptibility to cell death in B lymphocytes. EMBO Journal, 13(3), 683-691.