Positive selection on longevity-associated rodent branches
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB20584 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Removal of the transcription factor SAP1a member of the Ternary Complex Factor (TCF) group of transcription factors which in conjunction with Serum Response Factor (SRF) has been shown to have a profound effect on positive selection in the thymus. When another TCF Elk1 is knocked out in mice there is no effect on positive selection unless it is on a Sap1a KO background where the phenotype is very severe. We have stimulated isolated double positive T cells (DPs) with anti-CD3 to mimic positive selection and compared basal and stimulated transcription across the four genotypes to discover the downstream targets of Sap1a involved in positive selection.
2010-06-01 | GSE21546 | GEO
Project description:Removal of the transcription factor SAP1a member of the Ternary Complex Factor (TCF) group of transcription factors which in conjunction with Serum Response Factor (SRF) has been shown to have a profound effect on positive selection in the thymus. When another TCF Elk1 is knocked out in mice there is no effect on positive selection unless it is on a Sap1a KO background where the phenotype is very severe. We have stimulated isolated double positive T cells (DPs) with anti-CD3 to mimic positive selection and compared basal and stimulated transcription across the four genotypes to discover the downstream targets of Sap1a involved in positive selection. The Affymetrix mouse Chip Mouse430_2 arrays were used to define gene expression profiles in purified DPs with and with out CD3 treatment from 3 mice for each genotype (Wt,SapKO, ElkKO and SAP/Elk double KO)
2010-06-08 | E-GEOD-21546 | biostudies-arrayexpress
Project description:The ability of B-1 cells to become positively selected into the mature B cell pool, despite being weakly self-reactive, has puzzled the field since its initial discovery. Here, we explore changes in B cell positive selection as a function of developmental time by exploiting a link between CD5 surface levels and the natural occurrence of self-reactive B cell receptors (BCRs) in BCR wildtype mice. We show that the heterochronic RNA-binding protein Lin28b potentiates a neonatal mode of B cell selection characterized by enhanced overall positive selection and the developmental progression of CD5+ immature B cells in particular. Importantly, Lin28b achieves this through amplifying the CD19/PI3K/c-Myc positive feedback loop and ectopic Lin28b expression restores both positive selection and mature B cell numbers in CD19–/– adult mice. Thus, the temporally restricted expression of Lin28b alters the rules for B cell selection during ontogeny through modulating tonic signaling. We propose that this neonatal mode of B cell selection represents a cell intrinsic cue to accelerate the de novo establishment of the adaptive immune system and incorporate a layer of natural antibody mediated immunity throughout life.
2019-08-27 | GSE135603 | GEO
Project description:Sustained Ca2+ entry into CD4+CD8+ double-positive thymocytes is required for positive selection. We identified a voltage-gated Na+ channel (VGSC), essential for positive selection of CD4+ T cells. Pharmacological inhibition of VGSC activity inhibited sustained Ca2+ influx induced by positive-selecting ligands and in vitro positive selection of CD4+ but not CD8+ T cells. In vivo shRNA knockdown of Scn5a specifically inhibited positive selection of CD4+ T cells. Ectopic expression of VGSC in peripheral AND CD4+ T cells bestowed the ability to respond to a positively selecting ligand, directly demonstrating VGSC expression was responsible for increased sensitivity. Thus active VGSCs in thymocytes provides a mechanism by which a weak positive selecting signal can induce sustained Ca2+ signals required for CD4+ T cell development.
2012-07-01 | GSE38909 | GEO
Project description:Sustained Ca2+ entry into CD4+CD8+ double-positive thymocytes is required for positive selection. We identified a voltage-gated Na+ channel (VGSC), essential for positive selection of CD4+ T cells. Pharmacological inhibition of VGSC activity inhibited sustained Ca2+ influx induced by positive-selecting ligands and in vitro positive selection of CD4+ but not CD8+ T cells. In vivo shRNA knockdown of Scn5a specifically inhibited positive selection of CD4+ T cells. Ectopic expression of VGSC in peripheral AND CD4+ T cells bestowed the ability to respond to a positively selecting ligand, directly demonstrating VGSC expression was responsible for increased sensitivity. Thus active VGSCs in thymocytes provides a mechanism by which a weak positive selecting signal can induce sustained Ca2+ signals required for CD4+ T cell development. Pre-selected AND DP thymocytes were stimulated with plate bound peptide-loaded I-Ek Ig dimers. Genes were differentially regulated by positive and negative selection signals. The goal of this study is to identify ion-channel related genes critical for thymic positive selection, given the sustained Ca2+ entry into double positive thymocytes is required for positive selection. Total RNA of pre-selected AND thymocytes stimulated with I-Ek Ig dimers loaded with the positively-selecting peptide gp250, the negatively-selecting agonist peptide MCC, or the non-selecting control peptide Hb were used for the transcriptional profiling analysis. We found 28 genes were differentially down-regulated by MCC stimulation but upregulated by gp250 stimulation. One of them, scn4b, was ion-channel related.
2012-06-30 | E-GEOD-38909 | biostudies-arrayexpress
Project description:Developing B cells can differentiate into a variety of different subsets, but the mechanisms that determine these outcomes are incompletely understood, with theories based on separate lineages or the positive and negative selection by self-antigens. In particular, the development of the B-1 B cell subset arises mainly from precursors in early ontogeny and is subject to positive selection by self-antigens, whereas the follicular B-2 B cell subset arises later and is subject to negative control. In this study we show how a cell intrinsic switch from Lin28b to Let7 gene expression changes a B cell’s susceptibility from positive to negative selection during ontogeny. Ectopic expression of a Lin28b transgene in B cells restores the positive selection of autoreactive B-1 B cells by self-antigen in adult bone marrow. Analysis of antigen-specific immature B cells in early and late ontogeny identifies Lin28b-dependent genes associated with B-1 B cell development, including Arid3a and Bhleh41, and Lin28b-independent effects associated with the presence or absence of self-antigen. These findings identify cell intrinsic and extrinsic determinants of B cell fate during ontogeny and reconcile lineage and selection theories of B cell development. They explain how changes in the balance of positive and negative selection may be able to adapt to meet the immunological needs of an individual during its lifetime.
2020-02-26 | GSE135648 | GEO
Project description:Functional tuning of mature T cells based on their degree of self-reactivity is established during positive selection in the thymus, although how positive selection differs for thymocytes with relatively low versus high self-reactivity is unclear. In addition, preselection thymocytes are highly sensitive to low-affinity ligands, but the mechanism underlying their enhanced TCR sensitivity is not fully understood. Here we show that thymocytes with low self-reactivity experience briefer TCR signals and complete positive selection more slowly than those with high self-reactivity. Additionally, we provide evidence that cells with low self-reactivity retain a preselection gene expression signature as they mature, including genes previously implicated in modulating TCR sensitivity and a novel group of ion channel genes. Our results imply that thymocytes with low self-reactivity down-regulate TCR sensitivity more slowly during positive selection, and suggest that modulation of membrane ion channel function may play a role in regulating TCR tuning throughout development.
2021-01-16 | GSE164896 | GEO
Project description:We used RNA sequencing to characterize gene expression of Ly75+/+ B1-8hi and Ly75-/- B1-8hi B cells from the germinal center light zone (LZ) 12 h after forcing positive selection of the Ly75+/+ population with anti-DEC205-OVA.
2017-05-25 | GSE98778 | GEO
Project description:Developing B cells can differentiate into a variety of different subsets, but the mechanisms that determine these outcomes are incompletely understood, with theories based on separate lineages or the positive and negative selection by self-antigens. In particular, the development of the B-1 B cell subset arises mainly from precursors in early ontogeny and is subject to positive selection by self-antigens, whereas the follicular B-2 B cell subset arises later and is subject to negative control. In this study we show how a cell intrinsic switch from Lin28b to Let7 gene expression changes a B cell’s susceptibility from positive to negative selection during ontogeny. Ectopic expression of a Lin28b transgene in B cells restores the positive selection of autoreactive B-1 B cells by self-antigen in adult bone marrow. Analysis of antigen-specific immature B cells in early and late ontogeny identifies Lin28b-dependent genes associated with B-1 B cell development, including Arid3a and Bhleh41, and Lin28b-independent effects associated with the presence or absence of self-antigen. These findings identify cell intrinsic and extrinsic determinants of B cell fate during ontogeny and reconcile lineage and selection theories of B cell development. They explain how changes in the balance of positive and negative selection may be able to adapt to meet the immunological needs of an individual during its lifetime.
2020-02-26 | GSE135649 | GEO
Project description:Hap1 gene trap mutagenesis positive selection screen for HR factors
| PRJEB39032 | ENA