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PMID: 8467805 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Programmed cell death by bcl-2-dependent and independent mechanisms in B lymphoma cells.

The EMBO journal ·Vol. 12 ·No. 4 ·1993-04-00 ·Pages 1555-60

Cuende E, Alés-Martínez JE, Ding L, Gónzalez-García M, Martínez C, Nunez G

Abstract

Programmed cell death (PCD) or apoptosis is a common form of cellular demise during embryogenesis, tumorigenesis and clonal selection in the immune system. The bcl-2 proto-oncogene has been recently implicated as a potential physiological regulator of the PCD pathway. Gene transfer studies have shown that overexpression of bcl-2 blocks apoptosis mediated by several stimuli in cultured cell lines and promotes the survival of B and T lymphocytes in transgenic mice. However, it remains unclear whether under normal conditions bcl-2 is responsible for controlling cell death. We have investigated the role of bcl-2 in the antimembrane IgM (mIgM)-induced apoptotic death of WEHI-231 B cell lymphoma, a model that mimics clonal deletion of immature B cells by antigen. Signalling of mIgM receptors triggered downregulation of both bcl-2 RNA and protein, and induced apoptosis in WEHI-231 B cells. This effect appeared to be specific since (i) the levels of beta 2-microglobulin and beta-actin RNA remain unchanged and (ii) signalling of the apoptosis-resistant B cell lymphoma line BAL-17 with anti-mu was not associated with downregulation of bcl-2 RNA. However, stable expression of bcl-2 by transfection did not rescue WEHI-231 B cells from apoptosis, yet WEHI-231 cells overexpressing bcl-2 were more resistant to programmed cell death induced by heat-shock.(ABSTRACT TRUNCATED AT 250 WORDS)

Related Genes
MeSH Terms
Apoptosis B-Lymphocytes/physiology Gene Expression Regulation, Neoplastic Hot Temperature Humans Immunoglobulin M/physiology In Vitro Techniques Lymphoma, B-Cell/pathology Proto-Oncogene Mas Proto-Oncogene Proteins/physiology Proto-Oncogene Proteins c-bcl-2 RNA, Messenger/genetics Receptors, Antigen, B-Cell/physiology Tumor Cells, Cultured
Chemicals
Immunoglobulin M MAS1 protein, human Proto-Oncogene Mas Proto-Oncogene Proteins Proto-Oncogene Proteins c-bcl-2 RNA, Messenger Receptors, Antigen, B-Cell
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Cuende E
Centro de Biología Molecular (CSIC), Universidad Autónoma de Madrid, Spain.
Alés-Martínez J E
Ding L
Gónzalez-García M
Martínez C
Nunez G
References (44)
44 references, click to expand
  1. Differences in susceptibility of mature and immature mouse B lymphocytes to anti-immunoglobulin-induced immunoglobulin suppression in vitro. Possible implications for B-cell tolerance to self.
    J Exp Med. 1975 Nov 1;142(5):1052-64 PMID: 811748
  2. Mechanism of antigen-driven selection in germinal centres.
    Nature. 1989 Dec 21-28;342(6252):929-31 PMID: 2594086
  3. The regulation of growth and differentiation of a murine B cell lymphoma. II. The inhibition of WEHI 231 by anti-immunoglobulin antibodies.
    J Immunol. 1981 Jun;126(6):2466-9 PMID: 6785356
  4. A mouse IgM allotypic determinant (Igh-6.5) recognized by a monoclonal rat antibody.
    J Immunol. 1981 Sep;127(3):873-6 PMID: 6167630
  5. Purification of glutathione S-transferases by glutathione-affinity chromatography.
    Methods Enzymol. 1981;77:235-7 PMID: 7329302
  6. Structure of wild-type and mutant mouse beta 2-microglobulin genes.
    Cell. 1982 Jun;29(2):661-9 PMID: 6180834
  7. Mutations affecting programmed cell deaths in the nematode Caenorhabditis elegans.
    Science. 1983 Jun 17;220(4603):1277-9 PMID: 6857247
  8. Glucocorticoid activation of a calcium-dependent endonuclease in thymocyte nuclei leads to cell death.
    J Immunol. 1984 Jan;132(1):38-42 PMID: 6317746
  9. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays.
    J Immunol Methods. 1983 Dec 16;65(1-2):55-63 PMID: 6606682
  10. Cloning of the chromosome breakpoint of neoplastic B cells with the t(14;18) chromosome translocation.
    Science. 1984 Nov 30;226(4678):1097-9 PMID: 6093263
  11. Genetic control of programmed cell death in the nematode C. elegans.
    Cell. 1986 Mar 28;44(6):817-29 PMID: 3955651
  12. Deregulated Bcl-2-immunoglobulin transgene expands a resting but responsive immunoglobulin M and D-expressing B-cell population.
    Mol Cell Biol. 1990 May;10(5):1901-7 PMID: 2183011
  13. Deregulated Bcl-2 gene expression selectively prolongs survival of growth factor-deprived hemopoietic cell lines.
    J Immunol. 1990 May 1;144(9):3602-10 PMID: 2184193
  14. Induction of apoptosis (programmed cell death) in human leukemic HL-60 cells by inhibition of RNA or protein synthesis.
    J Immunol. 1990 Sep 15;145(6):1859-67 PMID: 2167911
  15. Anti-immunoglobulin antibodies induce apoptosis in immature B cell lymphomas.
    Eur J Immunol. 1990 Aug;20(8):1685-90 PMID: 2209683
  16. Novel primitive lymphoid tumours induced in transgenic mice by cooperation between myc and bcl-2.
    Nature. 1990 Nov 22;348(6299):331-3 PMID: 2250704
  17. Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death.
    Nature. 1990 Nov 22;348(6299):334-6 PMID: 2250705
  18. Anti-CD3-induced cell death in T cell hybridomas: mitochondrial failure and DNA fragmentation are distinct events.
    Eur J Immunol. 1991 Feb;21(2):419-24 PMID: 1825634
  19. Proliferation kinetics and the lifespan of B cells in central and peripheral lymphoid organs.
    Curr Opin Immunol. 1991 Apr;3(2):179-85 PMID: 2069745
  20. Drug-target interactions: only the first step in the commitment to a programmed cell death?
    Br J Cancer. 1991 Jul;64(1):192-6 PMID: 1854622
  21. Breakdown of self-tolerance in anergic B lymphocytes.
    Nature. 1991 Aug 8;352(6335):532-6 PMID: 1830923
  22. Germinal center cells express bcl-2 protein after activation by signals which prevent their entry into apoptosis.
    Eur J Immunol. 1991 Aug;21(8):1905-10 PMID: 1868875
  23. BCL2 protein is topographically restricted in tissues characterized by apoptotic cell death.
    Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):6961-5 PMID: 1871110
  24. Bcl-2 maintains B cell memory.
    Nature. 1991 Sep 5;353(6339):71-3 PMID: 1908951
  25. Clonal deletion of autospecific B lymphocytes.
    Immunol Rev. 1991 Aug;122:117-32 PMID: 1937539
  26. Self tolerance in the B-cell repertoire.
    Immunol Rev. 1991 Aug;122:5-19 PMID: 1937544
  27. Programmed cell death in the immune system.
    Adv Immunol. 1991;50:55-85 PMID: 1950799
  28. bcl-2 inhibits multiple forms of apoptosis but not negative selection in thymocytes.
    Cell. 1991 Nov 29;67(5):879-88 PMID: 1835668
  29. bcl-2 transgene inhibits T cell death and perturbs thymic self-censorship.
    Cell. 1991 Nov 29;67(5):889-99 PMID: 1959134
  30. Mechanisms and functions of cell death.
    Annu Rev Cell Biol. 1991;7:663-98 PMID: 1809356
  31. Prevention of B cell clonal deletion and anergy by activated T cells and their lymphokines.
    Semin Immunol. 1992 Jun;4(3):195-202 PMID: 1627790
  32. Inhibition of thymocyte apoptosis and negative antigenic selection in bcl-2 transgenic mice.
    Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):7003-7 PMID: 1495993
  33. Overexpressed full-length human BCL2 extends the survival of baculovirus-infected Sf9 insect cells.
    Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7295-9 PMID: 1502141
  34. Cooperative interaction between c-myc and bcl-2 proto-oncogenes.
    Nature. 1992 Oct 8;359(6395):554-6 PMID: 1406976
  35. Lymphoma models for B cell activation and tolerance. III. Cell cycle dependence for negative signalling of WEHI-231 B lymphoma cells by anti-mu.
    J Exp Med. 1986 Jul 1;164(1):156-64 PMID: 3487612
  36. Cloning and structural analysis of cDNAs for bcl-2 and a hybrid bcl-2/immunoglobulin transcript resulting from the t(14;18) translocation.
    Cell. 1986 Oct 10;47(1):19-28 PMID: 2875799
  37. Membrane IgM, IgD, and IgG act as signal transmission molecules in a series of B lymphomas.
    J Immunol. 1986 Oct 1;137(7):2162-7 PMID: 3020122
  38. Molecular analysis of mbcl-2: structure and expression of the murine gene homologous to the human gene involved in follicular lymphoma.
    Cell. 1987 May 22;49(4):455-63 PMID: 3032455
  39. Expression of the bcl-2 gene in mouse B lymphocytic cell lines is differentiation stage specific.
    Eur J Immunol. 1987 Apr;17(4):567-70 PMID: 3106072
  40. Expression of membrane interleukin 1 by fibroblasts transfected with murine pro-interleukin 1 alpha cDNA.
    Proc Natl Acad Sci U S A. 1988 Aug;85(15):5649-53 PMID: 3261013
  41. Single-step purification of polypeptides expressed in Escherichia coli as fusions with glutathione S-transferase.
    Gene. 1988 Jul 15;67(1):31-40 PMID: 3047011
  42. bcl-2-immunoglobulin transgenic mice demonstrate extended B cell survival and follicular lymphoproliferation.
    Cell. 1989 Apr 7;57(1):79-88 PMID: 2649247
  43. Stress-resistance conferred by high level of bcl-2 alpha protein in human B lymphoblastoid cell.
    Oncogene. 1989 Nov;4(11):1331-6 PMID: 2554236
  44. The structure of chromatin: interaction of ethidium bromide with native and denatured chromatin.
    Biochemistry. 1977 Feb 8;16(3):351-7 PMID: 836790
Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1993-04-00
Pages
1555-60
Language
English
Region
England
NLM ID
8208664
PMCID
PMC413368
Subset
IM
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