Abstract
Loss of dendritic cell potential is one of the major events in intrathymic T cell development, during which the progenitors become determined to the T cell lineage. However, it remains unclear whether this event occurs in synchrony with another important event, TCRbeta chain gene rearrangement, which has been considered the definitive sign of irreversible T cell lineage commitment. To address this issue, we used transgenic mice in which GFP expression is controlled by the lck proximal promoter. We found that the double-negative (DN) 2 stage can be subdivided into GFP- and GFP+ populations, representing functionally different developmental stages in that the GFP-DN2, but not GFP+DN2, cells retain dendritic cell potential. The GFP+DN2 cells were found to undergo several rounds of proliferation before the initiation of TCRbeta rearrangement as evidenced by the diversity of D-Jbeta rearrangements seen in T cells derived from a single GFP+DN2 progenitor. These results indicated that the determination step of progenitors to the T cell lineage is a separable event from TCRbeta rearrangement.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Differentiation / immunology
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Cell Division / genetics
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Cell Division / immunology
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Cell Lineage / immunology*
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Cells, Cultured
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Dendritic Cells / cytology
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Dendritic Cells / metabolism
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Down-Regulation / genetics
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Down-Regulation / immunology
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Gene Rearrangement, beta-Chain T-Cell Antigen Receptor*
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Green Fluorescent Proteins / biosynthesis
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Green Fluorescent Proteins / genetics
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Organ Culture Techniques
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Proto-Oncogene Proteins / antagonists & inhibitors
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Proto-Oncogene Proteins / biosynthesis
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Receptors, Antigen, T-Cell, alpha-beta / biosynthesis
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Receptors, Antigen, T-Cell, alpha-beta / genetics
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Stem Cells / cytology
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Stem Cells / immunology
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Stem Cells / metabolism
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T-Lymphocyte Subsets / cytology*
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T-Lymphocyte Subsets / immunology
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T-Lymphocyte Subsets / metabolism*
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Thymus Gland / cytology*
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Thymus Gland / immunology
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Thymus Gland / metabolism*
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Trans-Activators / antagonists & inhibitors
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Trans-Activators / biosynthesis
Substances
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Proto-Oncogene Proteins
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Receptors, Antigen, T-Cell, alpha-beta
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Trans-Activators
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proto-oncogene protein Spi-1
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Green Fluorescent Proteins