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Journal Articles Immunology Letters Year : 2006

The potential involvement of Notch signaling in NK cell development.

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Abstract

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.

Dates and versions

inserm-00473512 , version 1 (15-04-2010)

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Antonius G. Rolink, Gina Balciunaite, Corinne Demolière, Rhodri Ceredig. The potential involvement of Notch signaling in NK cell development.. Immunology Letters, 2006, 107 (1), pp.50-7. ⟨10.1016/j.imlet.2006.07.005⟩. ⟨inserm-00473512⟩

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