ArticleThe Journal of experimental medicine2001
The role of recombination activating gene (RAG) reinduction in thymocyte development in vivo.
Article in The Journal of experimental medicine, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 72 citations in OpenAlex.
- Dissecting cross-lineage tumourigenesis under p53 inactivation through single-cell multi-omics and spatial transcriptomics.Clinical and translational medicine · 2025Article
- Exosomes in review: A new frontier in CAR-T cell therapies.Neoplasia (New York, N.Y.) · 2025Review
- Unraveling the spatial organization and development of human thymocytes through integration of spatial transcriptomics and single-cell multi-omics profiling.Nature communications · 2024Article
- Transcriptomic profiling of thymic dysregulation and viral tropism after neonatal roseolovirus infection.Frontiers in immunology · 2024Article
- The Emerging Role of Induced Pluripotent Stem Cells as Adoptive Cellular Immunotherapeutics.Biology · 2023Review
- CRISPR-Cas9 engineering of the RAG2 locus via complete coding sequence replacement for therapeutic applications.Nature communications · 2023Article
- Multimodal human thymic profiling reveals trajectories and cellular milieu for T agonist selection.Frontiers in immunology · 2022Article
- Modeling of human T cell development in vitro as a read-out for hematopoietic stem cell multipotency.Biochemical Society transactions · 2021Review
- The Metabolic Landscape of Thymic T Cell DevelopmentFrontiers in immunology · 2021Article
- Characterization of an N-Terminal Non-Core Domain of RAG1 Gene Disrupted Syrian Hamster Model Generated by CRISPR Cas9.Viruses · 2018Article
- Yin Yang 1 Promotes Thymocyte Survival by Downregulating p53.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
- An anti-silencer- and SATB1-dependent chromatin hub regulates Rag1 and Rag2 gene expression during thymocyte development.The Journal of experimental medicine · 2015Article
- IL-7 coordinates proliferation, differentiation and Tcra recombination during thymocyte β-selection.Nature immunology · 2015Article
- Lineage-specific compaction of Tcrb requires a chromatin barrier to protect the function of a long-range tethering element.The Journal of experimental medicine · 2015Article
- Noncore RAG1 regions promote Vβ rearrangements and αβ T cell development by overcoming inherent inefficiency of Vβ recombination signal sequences.Journal of immunology (Baltimore, Md. : 1950) · 2014Article
- Global analysis of B cell selection using an immunoglobulin light chain-mediated model of autoreactivity.The Journal of experimental medicine · 2013Article
- The DNA damage- and transcription-associated protein paxip1 controls thymocyte development and emigration.Immunity · 2012Article
- Immune tolerance and transplantation.Seminars in oncology · 2012Review
- Lower TCR repertoire diversity in Traj18-deficient mice.Nature immunology · 2012Article
- Highly diverse TCRα chain repertoire of pre-immune CD8⁺ T cells reveals new insights in gene recombination.The EMBO journal · 2012Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Assembly of T cell receptor (TCR)alpha/beta genes by variable/diversity/joining (V[D]J) rearrangement is an ordered process beginning with recombination activating gene (RAG) expression and TCRbeta recombination in CD4(-)CD8(-)CD25(+) thymocytes. In these cells, TCRbeta expression leads to clonal expansion, RAG downregulation, and TCRbeta allelic exclusion. At the subsequent CD4(+)CD8(+) stage, RAG expression is reinduced and V(D)J recombination is initiated at the TCRalpha locus. This second wave of RAG expression is terminated upon expression of a positively selected alpha/beta TCR. To examine the physiologic role of the second wave of RAG expression, we analyzed mice that cannot reinduce RAG expression in CD4(+)CD8(+) T cells because the transgenic locus that directs RAG1 and RAG2 expression in these mice is missing a distal regulatory element essential for reinduction. In the absence of RAG reinduction we find normal numbers of CD4(+)CD8(+) cells but a 50-70% reduction in the number of mature CD4(+)CD8(-) and CD4(-)CD8(+) thymocytes. TCRalpha rearrangement is restricted to the 5' end of the Jalpha cluster and there is little apparent secondary TCRalpha recombination. Comparison of the TCRalpha genes expressed in wild-type or mutant mice shows that 65% of all alpha/beta T cells carry receptors that are normally assembled by secondary TCRalpha rearrangement. We conclude that RAG reinduction in CD4(+)CD8(+) thymocytes is not required for initial TCRalpha recombination but is essential for secondary TCRalpha recombination and that the majority of TCRalpha chains expressed in mature T cells are products of secondary recombination.
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