T cell receptor β chain gene rearrangement and selection during thymocyte development in adult mice

Dudley, Erastus C.; Petrie, Howard T.; Shah, Leena M.; Owen, Michael John; Hayday, Adrian

doi:10.1016/1074-7613(94)90102-3

Cited by 271 publications

(239 citation statements)

References 47 publications

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“…Cells that succeed in expressing TCRgd continue differentiating along this pathway, whereas cells that fail to do so die. Consistent with this interpretation is the recurrent (7,48,50,51), although not absolute (44), finding that a large fraction of TCRbchains present in gd cells from adult mice are functional, suggesting that their precursors were initially selected through the pre-TCR. Moreover, the presence of TCR-negative preapoptotic DN4 cells that have been b selected (52) is predicted by this interpretation.…”

Section: Discussionsupporting

confidence: 66%

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Temporal Predisposition to αβ and γδ T Cell Fates in the Thymus

Pereira

Boucontet

Cumano

2012

The Journal of Immunology

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How T cell progenitors engage into the γδ or αβ T cell lineages is a matter of intense debate. In this study, we analyzed the differentiation potential of single thymocytes from wild-type and TCRγδ-transgenic mice at two sequential early developmental stages. Double-negative (DN) 3 progenitors from both wild-type and transgenic mice retain the capacity to engage into both pathways, indicating that full commitment is only completed after this stage. More importantly, DN2 and DN3 progenitors from TCRγδ transgenic mice have strong biases for opposite fates, indicating that developmentally regulated changes, other than the production of a functional TCR, altered their likelihood to become a γδ or an αβ T cell. Thus, unlike the differentiation in other hematopoietic lineages, T cell progenitors did not restrict, but rather switch their differentiation potential as they developed.

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Section: Discussionsupporting

confidence: 66%

“…At this point, Vb to DJb rearrangements begin (6). Progression beyond the DN3 stage requires surface expression of either TCRgd or a pre-TCR (7,8), composed of a TCRb-chain paired with an invariant pre-TCRachain (9). Formation of a productive TCRgd allows the development of gd T cells that remain DN (8,10,11).…”

mentioning

confidence: 99%

Temporal Predisposition to αβ and γδ T Cell Fates in the Thymus

Pereira

Boucontet

Cumano

2012

The Journal of Immunology

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“…The pre-TCR (pT § / g ) expressed on DN thymocytes induces the expansion and differentiation into DP thymocytes, a process termed " g -selection" [2], and the targeted deletion of pT § results in the developmental block at the DN stage [3], as well as abrogating TCR g allelic exclusion [4]. In addition, the pre-TCR also commits immature thymocytes to the § g T cell lineage [3,5].…”

Section: Introductionmentioning

confidence: 99%

Impact of early expression of TCR α chain on thymocyte development

Huang

Kanagawa

2004

Eur J Immunol

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thymocytes expressing a transgenic T cell receptor (TCR) § chain have decreased capacity to give rise to CD4 + CD8 + thymocytes when compared with wild-type thymocytes. This inefficient CD4 -CD8 -to CD4 + CD8 + maturation is mediated by the transgenic TCR § chain pairing with endogenous TCR g chain but not with endogenous TCR + chain. Comparison between TCR § chain-transgenic mice with or without a functional pre-TCR § (pT § ) chain reveals that the formation of transgenic § /endogenous g TCR on CD4 -CD8 -thymocytes inhibits the formation of pre-TCR, but at the same time mediates CD4 -CD8 -to CD4 + CD8 + maturation in the absence of pre-TCR, albeit inefficiently. These results indicate that § g TCR and pre-TCR provide different signals for thymocyte development. They also suggest that the precise regulation of the sequential rearrangements of TCR g and § loci and the cellular expansion induced by the pre-TCR may both be evolved to ensure the efficient generation of mature § g T cells.

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“…We looked for differences in cell populations using PCR-fragment length polymorphism (PCR-FLP) analysis of DNA from FACSsorted BM cells (73). This assay consists of a PCR step using primers that amplify across the VDJ junction, followed by separation of the amplified products on a denaturing polyacrylamide gel, allowing an assessment of both CDR3 length heterogeneity and the distribution of in-frame and out-of-frame rearrangements within a population of cells.…”

Section: Recombinant Anv Marks Selected Pro-b and Immature B Cellsmentioning

confidence: 99%

Annexin V Binds to Positively Selected B Cells

Dillon

Constantinescu

Schlissel

2001

The Journal of Immunology

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Recombinant annexin V (rAnV) has been used in flow cytometry to identify cells undergoing apoptosis, based on its ability to bind to phosphatidylserine, a negatively charged lipid normally restricted to the cytoplasmic face of the plasma membrane but externalized early during apoptosis. When we stained murine bone marrow (BM) cells with fluorescently labeled rAnV, we found that a surprisingly large fraction of BM B cells bearing selectable transgenic Ag receptors bind significant amounts of rAnV, but that these cells are not apoptotic. Here, we show that binding of rAnV to developing B cells in normal mice correlates with B cell receptor-dependent selection events at several stages of development within both B-1 and B-2 cell subsets. In fact, nearly all B-1 B cells and splenic marginal zone B cells bind rAnV, suggesting that the externalization of phosphatidylserine occurs once mature B cells are selected through BCR-mediated signaling. However, this plasma membrane alteration is apparently not shared by all lymphocytes, because we did not find a parallel population of rAnV-binding viable T cells in vivo in normal or TCR transgenic mice. We also show that BM stromal cell lines can influence the extent of rAnV binding by viable BM B cells during coculture in vitro. We suggest that rAnV detects a potentially important membrane alteration that occurs as B cells develop in the BM and are readied for export to the peripheral lymphoid organs and again among mature B cells recruited to the marginal zone or the B-1 compartment.

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T cell receptor β chain gene rearrangement and selection during thymocyte development in adult mice

Cited by 271 publications

References 47 publications

Temporal Predisposition to αβ and γδ T Cell Fates in the Thymus

Temporal Predisposition to αβ and γδ T Cell Fates in the Thymus

Impact of early expression of TCR α chain on thymocyte development

Annexin V Binds to Positively Selected B Cells

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