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.
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.
Dannaeus
K
K
Department of Laboratory Medicine, Lund University, University Hospital MAS, Malmö, Sweden.
Johannisson
A
A
Nilsson
K
K
Jönsson
J I
JI
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
D015415:Biomarkers; D008024:Ligands; D016177:Macrophage-1 Antigen; D008565:Membrane Proteins; C084881:flt3 ligand protein; D017493:Leukocyte Common Antigens