Combined signaling through interleukin-7 receptors and flt3 but not c-kit potently and selectively promotes B-cell commitment and differentiation from uncommitted murine bone marrow progenitor cells

摘要: Multiple cytokines can synergize to stimulate the in vitro proliferation and exclusive myeloid differentiation of multipotent bone marrow progenitor cells. The ligand for c-kit (stem cell factor [SCF]) plays a key role stimulating erythroid production primitive hematopoietic progenitors. SCF combination with interleukin-7 (IL-7) also combined B-cell uncommitted cells as well growth early cells, although involvement B lymphopoiesis remains controversial. In present study, flt3-ligand (FL), which, other cytokines, has overlapping activities on from progenitors, was investigated its ability induce selective stroma-independent commitment Lin-Sca-1+ IL-7 alone did not any clonal FL gave rise few clusters ( 50 cells), whereas stimulation resulted 10% After 12 days incubation + IL-7, an almost 400-fold increase observed. Phenotyping showed that greater than 99% produced were lineage, they expressed B220, but surface markers specific myeloid, erythroid, or T-cell lineages. Furthermore, express cytoplasmic mu-heavy chain (cmu) IgM, positive CD24 (heat stable antigen [HSA]) CD43 (leukosialin), suggesting blocked at late pro-B-cell stage. Interestingly, all IL-7-responsive resulting pro-B c-kit, much more potent (62-fold) lineage. addition, selectively stimulated predominantly mature granulocytes. Replating studies progenitors committed because after 2 80% retained potential. As 27% remained 7 incubation, had lineage 10 IL-7. These results show potently synergizes enhance development