The Journal of Experimental Medicine
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Published online 18 December 2000.
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© The Rockefeller University Press, 0022-1007/2000/12/1775/ $5.00
The Journal of Experimental Medicine, Volume 192, Number 12, December 18, 2000 1775-1784

Original Article

Id2 and Id3 Inhibit Development of Cd34+ Stem Cells into Predendritic Cell (Pre-Dc)2 but Not into Pre-Dc1: Evidence for a Lymphoid Origin of Pre-Dc2



Hergen Spitsa, Franka Couwenberga, Arjen Q. Bakkera, Kees Weijera, and Christel H. Uittenbogaarta

a Division of Immunology, Netherlands Cancer Institute, 10066 CX Amsterdam, The Netherlands
Div. of Immunology, Netherlands Cancer Institute, Plesmanlaan 121, 10066 CX Amsterdam, Netherlands.31-20-512-205731-20-512-2063

hergen{at}nki.nl

We found previously that Id3, which inhibits transcriptional activities of many basic helix-loop-helix transcription factors, blocked T and B cell development but stimulated natural killer (NK) cell development. Here we report that ectopic expression of Id3 and another Id protein, Id2, strongly inhibited the development of primitive CD34+CD38– progenitor cells into CD123high dendritic cell (DC)2 precursors. In contrast, development of CD34+CD38– cells into CD4+CD14+ DC1 precursors and mature DC1 was not affected by ectopic Id2 or Id3 expression. These observations support the notion of a common origin of DC2 precursors, T and B cells. As Id proteins did not block development of NK cells, a model presents itself in which these proteins drive common lymphoid precursors to develop into NK cells by inhibiting their options to develop into T cells, B cells, and pre-DC2.

Key Words: dendritic cells • dendritic cell precursors • basic helix-loop-helix transcription factors • idiotype proteins • lymphoid development

C.H. Uittenbogaart's present address is the Dept. of Pediatrics, and the Department of Microbiology and Immunology, UCLA School of Medicine, Los Angeles, CA 90095-1747.

Abbreviations used in this paper: CLP, common lymphoid precursor; bHLH, basic helix-loop-helix; DC, dendritic cell; GFP, green fluorescent protein; HPRT, hypoxanthine ribosyltransferase; Id, inhibitor of DNA binding; {Delta}Id3, mutated Id3; IRES; internal ribosomal entry site; pDC, pre-DC; pT{alpha}, pre-TCR-{alpha}; SCF, stem cell factor.

© 2000 The Rockefeller University Press


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