title: Flt3 ligand induces the outgrowth of Mac-1+B220+ mouse bone marrow progenitor cells restricted to macrophage differentiation that coexpress early B cell-associated genes.
abstract: Flt3 ligand (FL) is an important cytokine that affects the proliferation of hematopoietic stem cells and multipotent progenitors. In addition, FL seems to be strongly involved in the differentiation of B cells and macrophages. These two cell types are derived from separate hematopoietic lineages and display distinct surface markers, for instance, the pan-B cell marker B220 (CD45R) and the myelo/monocytic marker Mac-1 (CD11b), respectively. However, reports during several years have shown that some lineage markers can be coexpressed on factor-dependent progenitor cells as well as on some malignant leukemic clones. In the present study, we describe the ability of FL to induce the development and growth of Mac-1+ progenitor cells coexpressing B220 from c-kit+Lin- mouse bone marrow cells. FL was shown to be necessary but not sufficient for the development of Mac-1(-)B220+ cells, because certain other cytokines, in particular IL-6, had to be added to the cultures. An extended characterization of the cells revealed coexpression of other early B-cell markers, i.e., CD24, CD43, and c-kit. They expressed transcripts for c-fms, the receptor for macrophage-colony stimulating factor (M-CSF), and were able to develop into macrophages at high numbers, but not to other myeloid cells. By RT-PCR analysis we could also demonstrate expression of the B-cell associated genes Pax-5, Rag-2, and TdT. In contrast, Mac-1(+)B220- cells from the same cultures did not express any of the B-cell genes, and retained a broader myeloid differentiation capacity. Despite these B-cell associated features, Mac-1(+)B220- cells could not be induced towards B-cell progenitors. Our data suggest that FL triggers the activation of some B-cell associated genes in progenitor cells predestined to macrophage differentiation.
authors.affiliation: Department of Laboratory Medicine, Lund University, University Hospital MAS, Malmö, Sweden.
authors.forename: K
authors.initials: K
authors.lastname: Dannaeus
authors.forename: A
authors.initials: A
authors.lastname: Johannisson
authors.forename: K
authors.initials: K
authors.lastname: Nilsson
authors.forename: J I
authors.initials: JI
authors.lastname: Jönsson
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology*; D015415:Biomarkers; D002454:Cell Differentiation / Q000187:drug effects; D019070:Cell Lineage; D005786:Gene Expression Regulation / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006801:Humans; D007223:Infant; D017493:Leukocyte Common Antigens / Q000276:immunology*; D008024:Ligands; D016177:Macrophage-1 Antigen / Q000276:immunology*; D008565:Membrane Proteins / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D015415:Biomarkers; D008024:Ligands; D016177:Macrophage-1 Antigen; D008565:Membrane Proteins; C084881:flt3 ligand protein; D017493:Leukocyte Common Antigens