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.
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.
Borzillo
G V
GV
Department of Tumor Cell Biology, St Jude Children's Research Hospital, Memphis, Tennessee 38105.
Endo
K
K
Tsujimoto
Y
Y
D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D015139:Blotting, Southern; D001853:Bone Marrow / Q000473:pathology; D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D005260:Female; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D015851:Interleukin-7 / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D019253:Proto-Oncogene Proteins c-bcl-2; D019089:Stem Cell Factor; D014161:Transduction, Genetic
D016298:Hematopoietic Cell Growth Factors; D015851:Interleukin-7; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D019089:Stem Cell Factor; D007371:Interferon-gamma