The Journal of Experimental Medicine
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Published online April 23, 2007
doi:10.1084/jem.20061959
The Journal of Experimental Medicine, Vol. 204, No. 5, 1119-1130
The Rockefeller University Press, 0022-1007 $30.00
© 2007 Boos et al.
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ARTICLE

Mature natural killer cell and lymphoid tissue–inducing cell development requires Id2-mediated suppression of E protein activity

Markus D. Boos1, Yoshifumi Yokota5, Gerard Eberl6, and Barbara L. Kee1,2,3,4

1 Committee on Immunology, 2 Committee on Cancer Biology, 3 Committe on Developmental Biology, and 4 Department of Pathology, University of Chicago, Chicago, IL 60657
5 Department of Molecular Genetics, School of Medicine, University of Fukui, Matsuoka, Fukui 910-1193, Japan
6 Laboratory of Lymphoid Tissue Development, Institut Pasteur, 75724 Paris Cedex 15, France

CORRESPONDENCE Barbara L. Kee: bkee{at}bsd.uchicago.edu

The Id2 transcriptional repressor is essential for development of natural killer (NK) cells, lymphoid tissue–inducing (LTi) cells, and secondary lymphoid tissues. Id2 was proposed to regulate NK and LTi lineage specification from multipotent progenitors through suppression of E proteins. We report that NK cell progenitors are not reduced in the bone marrow (BM) of Id2–/– mice, demonstrating that Id2 is not essential for NK lineage specification. Rather, Id2 is required for development of mature (m) NK cells. We define the mechanism by which Id2 functions by showing that a reduction in E protein activity, through deletion of E2A, overcomes the need for Id2 in development of BM mNK cells, LTi cells, and secondary lymphoid tissues. However, mNK cells are not restored in the blood or spleen of Id2–/–E2A–/– mice, suggesting a role for Id2 in suppression of alternative E proteins after maturation. Interestingly, the few splenic mNK cells in Id2–/– and Id2–/–E2A–/– mice have characteristics of thymus-derived NK cells, which develop in the absence of Id2, implying a differential requirement for Id2 in BM and thymic mNK development. Our findings redefine the essential functions of Id2 in lymphoid development and provide insight into the dynamic regulation of E and Id proteins during this process.


Abbreviations used: CLP, common lymphoid progenitor; EBF, early B cell factor; {gamma}c, {gamma} chain; i, immature; ICAM, intercellular adhesion molecule; LTi, lymphoid tissue–inducing; m, mature; NKP, NK cell progenitor; PP, Peyer's patch; QPCR, quantitative real-time PCR; VCAM, vascular cell adhesion molecule.


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