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.