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.
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 CD123(high) 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.
Spits
H
H
Division of Immunology, Netherlands Cancer Institute, 10066 CX Amsterdam, The Netherlands.
Couwenberg
F
F
Bakker
A Q
AQ
Weijer
K
K
Uittenbogaart
C H
CH
D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism*; D001402:B-Lymphocytes / Q000166:cytology; D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D018920:Coculture Techniques; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology; D005434:Flow Cytometry; D018507:Gene Expression Regulation, Developmental; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D051797:Inhibitor of Differentiation Protein 2; D051796:Inhibitor of Differentiation Proteins; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000196:embryology; D051379:Mice; D022423:Myeloid Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D009363:Neoplasm Proteins; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D012097:Repressor Proteins; D013601:T-Lymphocytes / Q000166:cytology; D013950:Thymus Gland / Q000166:cytology / Q000196:embryology / Q000276:immunology / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
D018952:Antigens, CD34; D004268:DNA-Binding Proteins; C497450:ID2 protein, human; C497452:Idb2 protein, mouse; D051797:Inhibitor of Differentiation Protein 2; D051796:Inhibitor of Differentiation Proteins; D009363:Neoplasm Proteins; D011994:Recombinant Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C075640:ID3 protein, human