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Transient Notch signaling induces NK cell potential in Pax5‐deficient pro‐B cells
Author(s) -
Carotta Sebastian,
Brady Jason,
Wu Li,
Nutt Stephen L.
Publication year - 2006
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.200636325
Subject(s) - biology , microbiology and biotechnology , notch signaling pathway , janus kinase 3 , progenitor cell , haematopoiesis , interleukin 21 , lymphopoiesis , cellular differentiation , lymphokine activated killer cell , cell , innate lymphoid cell , cytotoxic t cell , t cell , stem cell , immunology , signal transduction , antigen , in vitro , immune system , acquired immune system , genetics , gene
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 Pax5 –/– pro‐B cells that is strikingly similar to early thymopoiesis.