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.
Wu
L
L
The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia.
Nichogiannopoulou
A
A
Shortman
K
K
Georgopoulos
K
K
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D016827:CD8 Antigens / Q000032:analysis; D004268:DNA-Binding Proteins; D003713:Dendritic Cells / Q000166:cytology*; D017353:Gene Deletion; D051740:Ikaros Transcription Factor; D019891:Leukopoiesis; D008213:Lymphocyte Activation; D016131:Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011828:Radiation Chimera; D017384:Sequence Deletion; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D016827:CD8 Antigens; D004268:DNA-Binding Proteins; D014157:Transcription Factors; C497238:Zfpn1a1 protein, mouse; D051740:Ikaros Transcription Factor