Abnormalities of the Immune System Induced by Dysregulated bcl-2 Expression in Transgenic Mice (original) (raw)

Abstract

Dysregulated expression of the putative cellular oncogene _bcl_-2 by chromosomal translocation has been strongly implicated in follicular center B cell lymphoma, one of the most common hematologic malignancies in humans. These tumors usually contain a 14;18 chromosomal translocation (Fukuhara et al 1979) that juxtaposes _bcl_-2 with the immunoglobulin heavy chain (Igh) locus (Tsujimoto et al 1984; Cleary and Sklar 1985; Bakshi et al 1985). The recombination presumably subjects _bcl_-2 to the control of Igh regulatory sequences which enforce its constitutive expression in B lymphoid cells. The _bcl_-2 gene encodes a 24 kD non-glycosylated protein located on the cytoplasmic face of the plasma membrane (Tsujimoto et al 1987; Chen-Levy et al 1989). It is normally expressed in pre-B cells, quiescent in resting B cells, expressed again in activated B cells and then downregulated upon their terminal differentiation (Reed et al 1987; Gurfinkel et al 1987; Chen-Levy et al 1989). The first indication of the function of this putative oncogene was revealed by our previous studies on interleukin-3-dependent cell lines infected with a _bcl_-2 retrovirus. The cells survived withdrawal of growth factor, but entered a Go state, suggesting that constitutive _bcl_-2 expression promotes cell survival rather than proliferation (Vaux et al 1988).

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Authors and Affiliations

1. The Walter and Eliza Hall Institute of Medical Research, 3050, Melbourne, Australia
   A. Strasser, A. W. Harris, D. L. Vaux, E. Webb, M. L. Bath, J. M. Adams & S. Cory

Authors

1. A. Strasser
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2. A. W. Harris
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3. D. L. Vaux
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4. E. Webb
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5. M. L. Bath
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6. J. M. Adams
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7. S. Cory
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Editors and Affiliations

1. Laboratory of Genetics, National Institutes of Health, National Cancer Institute, Bethesda, MD, 20892, USA
   Michael Potter M.D.
2. Basel Institute for Immunology, Grenzacherstraße 487, CH-4005, Basel, Switzerland
   Fritz Melchers

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© 1990 Springer-Verlag Berlin Heidelberg

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Strasser, A. et al. (1990). Abnormalities of the Immune System Induced by Dysregulated _bcl_-2 Expression in Transgenic Mice. In: Potter, M., Melchers, F. (eds) Mechanisms in B-Cell Neoplasia 1990. Current Topics in Microbiology and Immunology, vol 166. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-75889-8\_22

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