title: Macrophage lineage switching of murine early pre-B lymphoid cells expressing transduced fms genes.
abstract: fms genes encoding either wild-type or constitutively activated colony-stimulating factor 1 receptors (CSF-1R) were introduced by retroviral infection into long-term mouse lymphoid cultures. Four early pre-B-cell lines transformed by the feline v-fms oncogene underwent spontaneous and irreversible differentiation to macrophages when transferred from RPMI 1640 to Iscove modified Dulbecco medium. Expression of wild-type human CSF-1R in early pre-B cells conferred no proliferative advantage unless human CSF-1 was added to the culture medium. A clonal, factor-dependent early pre-B-cell line (D1F9), selected for continuous growth on NIH 3T3 cell feeder layers producing human CSF-1, could be maintained in RPMI 1640 medium containing interleukin-7 (IL-7) but also differentiated to macrophages when grown in Iscove modified Dulbecco medium containing human CSF-1. The macrophages retained parental immunoglobulin gene rearrangements and proviral insertions, lost B-cell antigens, expressed butyrate esterase and MAC-1, were actively phagocytic, and no longer survived in IL-7. Unlike factor-independent v-fms transformants, the irreversible commitment of D1F9 cells to differentiate in the macrophage lineage could be suppressed by IL-7, depended on human (but not mouse) CSF-1, and was inhibited by an antibody to human CSF-1R. Signals mediated by transduced CSF-1R can therefore play a deterministic role in cell differentiation.
authors.affiliation: Department of Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105.
authors.forename: G V
authors.initials: GV
authors.lastname: Borzillo
authors.forename: R A
authors.initials: RA
authors.lastname: Ashmun
authors.forename: C J
authors.initials: CJ
authors.lastname: Sherr
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D001853:Bone Marrow / Q000378:metabolism; D002454:Cell Differentiation; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003115:Colony-Stimulating Factors / Q000494:pharmacology; D015321:Gene Rearrangement; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D015851:Interleukin-7 / Q000494:pharmacology; D016173:Macrophage Colony-Stimulating Factor; D008264:Macrophages / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016186:Receptor, Macrophage Colony-Stimulating Factor; D011956:Receptors, Cell Surface / Q000235:genetics*; D014161:Transduction, Genetic; D014162:Transfection
chemical_list: D003115:Colony-Stimulating Factors; D007143:Immunoglobulin Heavy Chains; D015851:Interleukin-7; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface; D016173:Macrophage Colony-Stimulating Factor; D016186:Receptor, Macrophage Colony-Stimulating Factor