The transcription factor Spi-B is expressed in plasmacytoid DC precursors and inhibits T-, B-, and NK-cell development.
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.
Schotte
Remko
R
Division of Immunology of the Netherlands Cancer Institute, Amsterdam, The Netherlands.
Rissoan
Marie-Clotilde
MC
Bendriss-Vermare
Nathalie
N
Bridon
Jean-Michel
JM
Duhen
Thomas
T
Weijer
Kees
K
Brière
Francine
F
Spits
Hergen
H
D017209:Apoptosis / Q000187:drug effects; D001402:B-Lymphocytes / Q000166:cytology; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D019070:Cell Lineage / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D003713:Dendritic Cells / Q000145:classification / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000166:cytology; D013601:T-Lymphocytes / Q000166:cytology; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D014161:Transduction, Genetic
D004268:DNA-Binding Proteins; D014157:Transcription Factors; C076877:SPIB protein, human