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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
Germline transcription from T-cell receptor Vbeta gene is uncoupled from allelic exclusion
Jingquan Jia1, Motonari Kondo, Yuan Zhuang
1Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
Abstract:
Allelic exclusion operates in B and T lymphocytes to ensure clonal expression of antigen receptors after V(D)J recombination. Germline transcription, which proceeds V(D)J recombination, has been postulated to provide an instructive signal for allelic exclusion. Here, we use a genetic marker to track germline transcription from a Vbeta gene within the TCRbeta locus. We find that developing thymocytes exhibit uniformed, bi-allelic activation of the Vbeta gene before V-DJ recombination, a process subject to allelic exclusion. We further show that V-DJ rearrangement promotes activation rather than silencing of germline transcription from the remaining Vbeta genes on either the functionally or non-functionally rearranged chromosome. Results presented here suggest that germline transcription, although necessary for V(D)J recombination, is not sufficient to instruct allelic exclusion.
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