Commitment to natural killer cells requires the helix–loop–helix inhibitor Id2

Abstract

We have previously described how T and natural killer (NK) lineage commitment proceeds from common T͞NK progenitors (p-T͞NK) in the murine fetal thymus (FT), with the use of a clonal assay system capable of discriminating p-T͞NK from unipotent T or NK lineagecommitted progenitors (p-T and p-NK, respectively). The molecular mechanisms controlling the commitment processes, however, are yet to be defined. In this study, we investigated the progenitor activity of FT cells from Id2 ؊/؊ mice that exhibit defective NK cell development. In the Id2 ؊/؊ FT, NK cells were greatly reduced, and a cell population that exclusively contains p-NK in the wild-type thymus was completely missing. Id2 ؊/؊ FT progenitors were unable to differentiate into NK cells in IL-2-supplemented-FT organ culture. Single progenitor analysis demonstrated that all Id2 ؊/؊ fetal thymic progenitors are destined for the T cell lineage, whereas progenitors for T͞NK, T, and NK cell lineages were found in the control. Interestingly, the total progenitor number was similar between Id2 ؊/؊ and Id2 ؉/؉ embryos analyzed. Expression of Id2 was correlated with p-NK activity. Our results suggest that Id2 is indispensable in thymic NK cell development, where it most probably restricts bipotent T͞NK progenitors to the NK cell lineage.basic helix-loop-helix transcription factor ͉ clonal assay ͉ progenitor ͉ T cell ͉ fetal thymus

Expression of chondrogenic potential of mouse trunk neural crest cells by FGF2 treatment

“…Cycle numbers were determined to be in the linear range for Id2 and ␤-actin. The following primer sets were used: Id2 primer set, 5Ј primer 5Ј-TCTGAGCTTATGTCGA-ATGATAGC-3Ј and 3Ј primer 5Ј-CA-CAGCATTCAGTAGGCTCGTGTC-3Ј, which amplifies a 498-bp fragment (Ikawa et al, 2001); and ␤-actin primer set, 5Ј primer 5Ј-GTGGGC-CGCTCTAGGCACCAA-3Ј and 3Ј primer 5Ј-CTCTTTGATGTCACGCA-CGATTTC-3Ј, which amplifies a 540-bp fragment (Alonso et al, 1986). The content of PCR products specific for Id2 was estimated from the staining intensities of the specific bands using Kodak EDAS 290 image analysis software.…”

Id and development

“…How does Id2 participate in the development of these unique cells? Defective development of the cells in the absence of Id2 implies that inhibition of the activity of bHLH factors is important for the di erentiation of these cells from a progenitor as seen for NK cell development (Ikawa et al, 2001). The responsible factor must play a role in supporting and maintaining the main¯ow of developing cells in the lymphoid lineage, although it is not clear what kind of bHLH factor is involved in this process.…”

“…Among the most immature CD44+CD257 fetal thymocytes, they further identi®ed a CD122 (IL-2Rb)-positive subfraction that exclusively contains progenitors committed to become NK lineage cells. Analysis of NK cells in the fetal thymus of Id27/7 mice has revealed a role for Id2 in a cell fate decision (Ikawa et al, 2001). In Id27/7 fetal thymi, thymic NK cells are reduced as in the adult organs and Id27/7 fetal thymocytes show little di erentiation into NK cells even in conditions containing cytokines that are highly supportive for NK cells in this system.…”

Differential and Nonredundant Roles of Phospholipase Cγ2 and Phospholipase Cγ1 in the Terminal Maturation of NK Cells

“…Committed NKPs have been preferentially identified in the BM and in thymus (17,52). Cytokines such as GM-CSF, IL-7, IL-15, and IL-21 generated in the microenvironment play a critical role in the initiation and sustenance of NK cell development through IL-15R␣, IL-2/IL-15R␤ (CD122), and c-Kit (CD117) receptors (37).…”