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Prepublished online as a Blood First Edition Paper on September 19, 2002; DOI 10.1182/blood-2002-02-0438.

Submitted February 8, 2002
Accepted September 4, 2002
The transcription factor Spi-B is expressed in plasmacytoid DC precursors and inhibits T, B, and NK cell development
Remko Schotte, Marie-Clotilde Rissoan, Nathalie Bendriss-Vermare, Jean-Michel Bridon, Thomas Duhen, Kees Weijer, Francine Briere, and Hergen Spits*
Division of Immunology, Netherlands Cancer Institute, Amsterdam, The Netherlands
Laboratory for Immunological Research, Schering Plough, Dardilly, France
* Corresponding author; email: h.spits{at}nki.nl.
Human plasmacytoid DC also called type 2 dendritic cell precursors or natural IFN-producing cells represent a cell type with distinctive phenotypic and functional features. They are present in the thymus and probably share a common precursor with T and NK cells. In an effort to identify genes that control pDC development we searched for genes of which the expression is restricted to human pDC using a cDNA subtraction technique with activated monocyte-derived DC as competitor. We identified the transcription factor Spi-B to be expressed in pDC but not in Mo-DC. Spi-B expression in pDC was maintained upon in vitro-maturation of pDC. Spi-B was expressed in early CD34+CD38- hematopoietic progenitors and in CD34+CD1a- thymic precursors. Spi-B expression is downregulated when uncommitted CD34+CD1a- thymic precursors differentiate into committed CD34+CD1a+ pre T cells. Overexpression of Spi-B in hematopoietic progenitor cells resulted in inhibition of development of T cells both in vitro and in vivo. In addition, development of progenitor cells into B and NK cells in vitro was also inhibited by Spi-B overexpression. Our results indicate that Spi-B is involved in the control of pDC development by limiting the capacity of progenitor cells to develop into other lymphoid lineages.

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