%0 Journal Article %T The potential involvement of Notch signaling in NK cell development. %+ Developmental and Molecular Immunology, Department of Clinical and Biological Sciences (DKBW) %+ Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT) %A Rolink, Antonius, G. %A Balciunaite, Gina %A Demolière, Corinne %A Ceredig, Rhodri %< avec comité de lecture %@ 0165-2478 %J Immunology Letters %I Elsevier %V 107 %N 1 %P 50-7 %8 2006-09-15 %D 2006 %R 10.1016/j.imlet.2006.07.005 %M 16930724 %Z Life Sciences [q-bio]/ImmunologyJournal articles %X NK cells constitute an essential element of the innate immune system; however, the cellular and molecular mechanisms that guide their early development are still poorly understood. Here, we demonstrate that in addition to its known crucial role in T cell development, Notch signaling can also be involved in NK cell development. Thus, upon co-culture on OP9 stroma expressing the Notch ligand Delta-like 1 (OP9-DL1), Pax5-deficient pro-B cells, which have multi-lineage potential, efficiently differentiate into T and NK cells. Upon DL-1 signaling, Pax5-deficient pro-B cells down-regulate both surface CD93 expression and transcripts for B cell-specific genes and concomitantly up-regulate T lineage gene transcripts. Subsequent transfer of DL-1-signaled Pax5-deficient pro-B cells onto OP9 stroma in the presence of IL-2 leads to their efficient differentiation into NK1.1(+), functional NK cells. Moreover, bone marrow early progenitor with lymphoid and myeloid differentiation potential (EPLM), which we have previously described as the normal in vivo-equivalent of Pax5-deficient pro-B cells, also gain the ability to differentiate into effector NK cells following transient DL1 Notch-mediated signaling. The potential involvement of Notch signaling in the generation of the NK cell repertoire in vivo is discussed. %G English %L inserm-00473512 %U https://inserm.hal.science/inserm-00473512 %~ INSERM %~ UNIV-FCOMTE