| First Author | Carotta S | Year | 2006 |
| Journal | Eur J Immunol | Volume | 36 |
| Issue | 12 | Pages | 3294-304 |
| PubMed ID | 17111353 | Mgi Jnum | J:117084 |
| Mgi Id | MGI:3695549 | Doi | 10.1002/eji.200636325 |
| Citation | Carotta S, et al. (2006) Transient Notch signaling induces NK cell potential in Pax5-deficient pro-B cells. Eur J Immunol 36(12):3294-304 |
| abstractText | Unlike early B/T cell development, NK cell lineage commitment is not well understood, with a major limitation being the lack of a robust culture system to assay NK cell progenitors. Here we have exploited the multi-lineage potential of Pax5(-/-) pro-B cells to establish an effective system to direct differentiation of progenitors into the NK cell lineage. Cultivation of Pax5(-/-) pro-B cells on OP9 cells expressing the Notch ligand Delta-Like1 (OP9-DL1) in the presence of IL-7 efficiently induced T and NK cell potential. For NK cells, Notch was only transiently required, as prolonged signaling decreased NK and increased T cell development. Pure NK cell populations could be obtained by the culture of these Notch signal-experienced cells onto OP9 stroma and IL-15. A similar transient exposure to Notch was also compatible with the differentiation of NK cells from hematopoietic progenitors, while sustained Notch signaling impaired NK cell generation. Pax5(-/-) pro-B cell-derived NK cells were cytotoxic, secreted cytokines and expressed all the expected NK cell-specific surface markers examined except the Ly49 family, a phenotype similar to fetal NK cells. These data indicate that Notch signaling induces T/NK cell differentiation in Pax5(-/-) pro-B cells that is strikingly similar to early thymopoiesis. |
