T cell lineage determination precedes the initiation of TCR beta gene rearrangement.
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.
Masuda
Kyoko
K
Laboratory for Lymphocyte Development, RIKEN Research Center for Allergy and Immunology, Yokohama, Japan.
Kakugawa
Kiyokazu
K
Nakayama
Toshinori
T
Minato
Nagahiro
N
Katsura
Yoshimoto
Y
Kawamoto
Hiroshi
H
D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D019070:Cell Lineage / Q000276:immunology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009924:Organ Culture Techniques; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis / Q000235:genetics; D013234:Stem Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D015534:Trans-Activators / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D000099232:Proto-Oncogene Protein Spi-1