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Prepublished online as a Blood First Edition Paper on September 19, 2002; DOI 10.1182/blood-2002-02-0438.
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Blood, 1 February 2003, Vol. 101, No. 3, pp. 1015-1023
IMMUNOBIOLOGY
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 Brière, and
Hergen Spits
From the Division of Immunology of the Netherlands
Cancer Institute, Amsterdam, The Netherlands; and Schering
Plough Laboratory for Immunological Research, Dardilly,
France.
Human plasmacytoid dendritic cells (pDCs), also called type 2 dendritic cell precursors or natural interferon (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 natural killer (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 DCs (Mo-DCs) as
competitor. We identified the transcription factor Spi-B to be
expressed in pDCs but not in Mo-DCs. Spi-B expression in pDCs was
maintained on in vitro maturation of pDCs. Spi-B was expressed in
early CD34+CD38 hematopoietic progenitors and
in CD34+CD1a thymic precursors. Spi-B
expression is down-regulated 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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