Cell-autonomous defects in dendritic cell populations of Ikaros mutant mice point to a developmental relationship with the lymphoid lineage.

The transcription factor Ikaros is a major determinant of lymphocyte differentiation. Mice homozygous for an Ikaros dominant-negative (DN-/-) mutation lack all cells of lymphoid origin, including T, B, and natural killer (NK) cells. Mice homozygous for an Ikaros null allele lack B and NK cells but display specific defects in T lymphocytes. Nonetheless, both Ikaros mutant lines make an excess of monocytes and macrophages. Here we report that the production of subsets of antigen-presenting dendritic cells (DCs) is also defective. By constructing bone marrow chimeras, we demonstrate that the Ikaros-mediated defect in lymphocytes and DCs is intrinsic to their precursors and is not environment dependent. The selective defects in DCs manifested with the Ikaros null mutation suggest a tight linkage between development of T cells and CD8alpha+ DCs. The complete lack of DCs in the lymphoid organs of Ikaros DN-/- micke points to an essential role for the Ikaros gene family in the development of all DCs.