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PMID:1373874

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Citation

Borzillo, GV, Endo, K and Tsujimoto, Y (1992) Bcl-2 confers growth and survival advantage to interleukin 7-dependent early pre-B cells which become factor independent by a multistep process in culture. Oncogene 7:869-76

Abstract

Early pre-B cells derived from mouse lymphoid bone marrow cultures were expanded on a surrogate stromal cell line composed of NIH3T3 fibroblasts engineered to secrete interleukin 7 (IL-7). Three immortal, IL-7-dependent cell lines were generated and infected with recombinant retroviruses to determine the effects of the human follicular B-cell lymphoma gene, bcl-2, on immature stages of B-cell development. Cells expressing bcl-2 grew at rates similar to those of control (vector only) cells when plated on bone marrow stromal lines, but exhibited a c. two-fold net proliferative advantage when grown in liquid medium supplemented with IL-7 alone. Bcl-2 prevented apoptosis when the infected early pre-B-cell lines were deprived of IL-7 and other growth factors provided by stromal cells. Following factor deprivation, a subset of cells expressing bcl-2 survived indefinitely. Two such cultures spontaneously gave rise to factor-independent variants which grew slowly in unsupplemented liquid culture and formed agar colonies, yet still responded positively to IL-7 and kit ligand, and negatively to gamma-interferon. Bcl-2 thus provides a survival capacity and modest growth advantage to early pre-B cells, which may recapitulate its effects in human B cells bearing t(14;18) translocations and ultimately contribute to transformation.

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PubMed

Keywords

Animals; B-Lymphocytes/physiology; Blotting, Southern; Bone Marrow/pathology; Cell Division/drug effects; Cell Division/genetics; Cell Survival/drug effects; Cell Survival/genetics; Cell Transformation, Neoplastic/genetics; Cells, Cultured; Colony-Forming Units Assay; Female; Hematopoietic Cell Growth Factors/pharmacology; Interferon-gamma/pharmacology; Interleukin-7/physiology; Mice; Mice, Inbred BALB C; Proto-Oncogene Proteins/genetics; Proto-Oncogene Proteins c-bcl-2; Stem Cell Factor; Transduction, Genetic

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