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  • Title: 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.
    Author: Borzillo GV, Endo K, Tsujimoto Y.
    Journal: Oncogene; 1992 May; 7(5):869-76. PubMed ID: 1373874.
    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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