Clonal lymphoid progenitor cell lines expressing the BCR/ABL oncogene retain full differentiative function.
The early stages of hematopoiesis have been difficult to study due to problems in obtaining homogeneous populations of progenitor cells that retain both self-renewal and differentiative capacities. We have developed an in vitro system in which transformation of murine bone-marrow cells with the BCR/ABL oncogene, a gene associated with stem-cell leukemias, leads to the outgrowth of clonal lines that have an early lymphoid progenitor cell phenotype. The progenitor cells retain immunoglobulin heavy and light chain genes in a germ-line configuration. These cells give rise in vitro to pre-B cells that have diverse diversity-joining (D-J) region rearrangements, and on transfer to mice with severe combined immune deficiency, differentiate to surface IgM+, immunoglobulin-secreting B cells that respond to T-cell help and function in an antigen-specific fashion. Although their growth is stimulated by BCR/ABL, the progenitor cells depend for continued growth on a stromal cell-derived soluble factor distinct from the pre-B-cell growth factor, interleukin 7. These findings show that BCR/ABL can promote proliferation of an early hematopoietic progenitor cell without preventing its differentiation. This system provides a means of studying the complete B-cell developmental process from clonal progenitor cell to end-stage plasma cell.
Department of Microbiology, University of California, Los Angeles 90024.
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Scherle
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K
Dorshkind
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ON
Witte
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D001853:Bone Marrow / Q000276:immunology; D002454:Cell Differentiation; D002460:Cell Line; D002478:Cells, Cultured; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D007153:Immunologic Deficiency Syndromes / Q000235:genetics / Q000276:immunology; D015851:Interleukin-7 / Q000494:pharmacology; D008214:Lymphocytes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D009154:Mutation; D009857:Oncogenes
D015851:Interleukin-7; D016044:Fusion Proteins, bcr-abl