The transcription factor Spi-B is expressed in plasmacytoid DC precursors and inhibits T-, B-, and NK-cell development

• Published in: Blood Vol. 101; no. 3; pp. 1015 - 1023
• Main Authors: Schotte, Remko, Rissoan, Marie-Clotilde, Bendriss-Vermare, Nathalie, Bridon, Jean-Michel, Duhen, Thomas, Weijer, Kees, Brière, Francine, Spits, Hergen
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 01.02.2003; The Americain Society of Hematology
• Subjects: Apoptosis - drug effects; B-Lymphocytes - cytology; Biological and medical sciences; Cell Differentiation - drug effects; Cell Division - drug effects; Cell Lineage - drug effects; Dendritic Cells - classification; Dendritic Cells - cytology; Dendritic Cells - metabolism; DNA-Binding Proteins - analysis; DNA-Binding Proteins - genetics; DNA-Binding Proteins - physiology; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Humans; Immunobiology; Immunophenotyping; Killer Cells, Natural - cytology; Lymphoid cells: ontogeny, maturation, markers, receptors, circulation and recirculation; T-Lymphocytes - cytology; Transcription Factors - analysis; Transcription Factors - genetics; Transcription Factors - physiology; Transduction, Genetic; Natural killer cell; Signal transduction; Transcription factor Spi-B; Precursor cell; T-Lymphocyte; Cellular immunity; B-Lymphocyte; Inhibition; Cell differentiation; Transcription factor; Plasmatoid dendritic cell
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2002-02-0438

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.