Extrathymic development of V alpha 14-positive T cells.
It is known that rearrangement of the T cell antigen receptor (TCR) gene occurs in the thymus during T cell development and consequently results both in the deletion of DNA between the variable (V) and diversity/joining segments and in the formation of a circular DNA with recombination signal sequences. Here, we provide evidence that V alpha 14+ TCR gene rearrangements take place in extrathymic sites, such as bone marrow, liver, and intestine, but not in spleen, because we were able to detect frequent productive and nonproductive V alpha 14+ coding and signal sequences as a result of TCR rearrangements in extrathymic sites. Similar findings were also detected in athymic mice. Quantitative analysis shows that the relative amounts of V alpha 14 gene-mediated signal sequences in extrathymic tissues are higher than those in thymus. On the contrary, TCR rearrangements of V alpha 1.1 T cells, which are known to develop in the thymus, were mainly detected in the thymus, Peyer's patch, and spleen, but not in other extrathymic tissues, showing patterns distinct from V alpha 14 TCR rearrangements. These findings are evidence of extrathymic development of V alpha 14+ T cells. Differential characteristic TCR rearrangement patterns also indicate that distinct TCR repertoires are generated in different lymphoid tissues.
Division of Molecular Immunology, School of Medicine, Chiba University, Japan.
Y
Y
Makino
N
N
Yamagata
T
T
Sasho
Y
Y
Adachi
R
R
Kanno
H
H
Koseki
M
M
Kanno
M
M
Taniguchi
D000818:Animals; D001483:Base Sequence; D001853:Bone Marrow / Q000276:immunology; D001854:Bone Marrow Cells; D004247:DNA; D004268:DNA-Binding Proteins; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor; D018398:Homeodomain Proteins; D008099:Liver / Q000166:cytology / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D021382:Protein Sorting Signals / Q000235:genetics; D011506:Proteins / Q000235:genetics; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology
D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D021382:Protein Sorting Signals; D011506:Proteins; C499308:Rag2 protein, mouse; D016693:Receptors, Antigen, T-Cell, alpha-beta; C064655:V(D)J recombination activating protein 2; C064658:RAG-1 protein; D004247:DNA