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Streamlined Single Cell TCR Isolation and Generation of Retroviral Vectors for In Vitro and In Vivo Expression of Human TCRs
Published on: September 10, 2017
Expression of T-cell receptor genes during early T-cell development
Janice L Abbey1, Helen C O'Neill
1School of Biochemistry and Molecular Biology, The Australian National University, Canberra, ACT, Australia.
Germline transcription, previously thought purposeless, is a regulated process in lymphoid cell development. These transcripts may play a functional role or serve as markers for early lymphoid progenitors.
Area of Science:
- Immunology
- Developmental Biology
- Molecular Genetics
Background:
- Lymphoid cell development involves T-cell receptor (TCR) and immunoglobulin (Ig) gene rearrangement.
- Germline transcripts from these loci were historically considered non-functional byproducts of VDJ recombination.
- Their association with open chromatin during rearrangement was the accepted explanation for their presence in early progenitors.
Purpose of the Study:
- To investigate the role and regulation of germline transcription in lymphoid development.
- To determine if germline transcripts have functions beyond being markers.
- To re-evaluate the association of germline transcription with VDJ recombination.
Main Methods:
- Analysis of germline TCR-V beta 8.2 transcripts.
- Study of RAG(-/-) mice lacking VDJ recombination and recombinase activity.
- Observation of lymphoid cell development and gene expression patterns.
Main Results:
- Germline TCR-V beta 8.2 transcripts were identified in RAG(-/-) mice, independent of VDJ rearrangement.
- This finding challenges the direct link between germline transcription and the VDJ recombination process.
- Evidence suggests germline TCR-V beta transcription is a developmentally regulated phenomenon.
Conclusions:
- Germline transcription in lymphoid cells is a regulated developmental event, not solely tied to VDJ recombination.
- These transcripts may possess functional roles in lymphoid cell development.
- Germline transcripts can serve as reliable markers for early lymphoid progenitors.
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