Transient Notch signaling induces NK cell potential in Pax5-deficient pro-B cells

Carotta, S; Brady, J; Wu, L; Nutt, SL

Author(s): Carotta, S; Brady, J; Wu, L; Nutt, SL;
Details: Publication Year 2006-12,Volume 36,Issue #12,Page 3294-3304
Journal Title: EUROPEAN JOURNAL OF IMMUNOLOGY
Publication Type: Journal Article
Abstract: 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 PaxS5(-/-) pro-B cells that is strikingly similar to early thymopoiesis.
Publisher: WILEY-V C H VERLAG GMBH
Keywords: EMBRYONIC STEM-CELLS; NATURAL-KILLER-CELL; T-CELL; BONE-MARROW; IN-VITRO; LYMPHOID PROGENITORS; HEMATOPOIETIC PROGENITOR; FETAL LIVER; DIFFERENTIATION; LINEAGE
Publisher's Version: https://doi.org/10.1002/eji.2006363251
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2006-12-01 12:00:00