ArticleJournal of immunology (Baltimore, Md. : 1950)2011
Differential regulation of proximal and distal Vbeta segments upstream of a functional VDJbeta1 rearrangement upon beta-selection.
Article in Journal of immunology (Baltimore, Md. : 1950), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 10 citations in OpenAlex.
- The Cyclin D3 Protein Enforces Monogenic TCRβ Expression by Mediating TCRβ Protein-Signaled Feedback Inhibition of Vβ Recombination.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Domain-Specific and Stage-Intrinsic Changes in Tcrb Conformation during Thymocyte Development.Journal of immunology (Baltimore, Md. : 1950) · 2015Article
- Placing ion channels into a signaling network of T cells: from maturing thymocytes to healthy T lymphocytes or leukemic T lymphoblasts.BioMed research international · 2015Review
- The ataxia telangiectasia mutated and cyclin D3 proteins cooperate to help enforce TCRβ and IgH allelic exclusion.Journal of immunology (Baltimore, Md. : 1950) · 2014Article
- 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
- Allelic exclusion of the immunoglobulin heavy chain locus is independent of its nuclear localization in mature B cells.Nucleic acids research · 2013Article
- Requirement for dicer in survival of proliferating thymocytes experiencing DNA double-strand breaks.Journal of immunology (Baltimore, Md. : 1950) · 2013Article
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
Developmental stage-specific regulation of transcriptional accessibility helps control V(D)J recombination. Vβ segments on unrearranged TCRβ alleles are accessible in CD4(-)/CD8(-) (double-negative [DN]) thymocytes, when they recombine, and inaccessible in CD4(+)/CD8(+) (double-positive [DP]) thymocytes, when they do not rearrange. Downregulation of Vβ accessibility on unrearranged alleles is linked with Lat-dependent β-selection signals that inhibit Vβ rearrangement, stimulate Ccnd3-driven proliferation, and promote DN-to-DP differentiation. Transcription and recombination of Vβs on VDJβ-rearranged alleles in DN cells has not been studied; Vβs upstream of functional VDJβ rearrangements have been found to remain accessible, yet not recombine, in DP cells. To elucidate contributions of β-selection signals in regulating Vβ transcription and recombination on VDJβ-rearranged alleles, we analyzed wild-type, Ccnd3(-/-), and Lat(-/-) mice containing a preassembled functional Vβ1DJCβ1 (Vβ1(NT)) gene. Vβ10 segments located just upstream of this VDJCβ1 gene were the predominant germline Vβs that rearranged in Vβ1(NT/NT) and Vβ1(NT/NT)Ccnd3(-/-) thymocytes, whereas Vβ4 and Vβ16 segments located further upstream rearranged at similar levels as Vβ10 in Vβ1(NT/NT)Lat(-/-) DN cells. We previously showed that Vβ4 and Vβ16, but not Vβ10, are transcribed on Vβ1(NT) alleles in DP thymocytes; we now demonstrate that Vβ4, Vβ16, and Vβ10 are transcribed at similar levels in Vβ1(NT/NT)Lat(-/-) DN cells. These observations indicate that suppression of Vβ rearrangements is not dependent on Ccnd3-driven proliferation, and DN residence can influence the repertoire of Vβs that recombine on alleles containing an assembled VDJCβ1 gene. Our findings also reveal that β-selection can differentially silence rearrangement of germline Vβ segments located proximal and distal to functional VDJβ genes.
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