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GSE11556
Mus musculus
10 Downloadable Samples
Affymetrix Murine Genome U74A Array (mgu74a), Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2), Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Autoregulation of Th1-mediated inflammation by twist1.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2), Affymetrix Murine Genome U74A Array (mgu74a)
Description
Gene expression profiling of repeatedly activated compared to recently activated Th1 cells to identify genes that play a role in chronic inflammatory disorders and may qualify as diagnostic or therapeutic targets;
Publication Title
Autoregulation of Th1-mediated inflammation by twist1.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
The basic helix-loop-helix transcriptional repressor twist1, as an antagonist of nuclear factor B (NF-B)-dependent cytokine expression, is involved in the regulation of inflammation-induced immunopathology. We could show that twist1 is expressed by activated T helper (Th) 1 effector memory cells. Induction of twist1 in Th cells is dependent on NF-B, nuclear factor of activated T cells (NFAT), and interleukin (IL)-12 signaling via signal transducer and activator of transcription (STAT) 4. Expression of twist1 is transient following T-cell receptor engagement, and increases upon repeated stimulation of Th1 cells. Imprinting for enhanced twist1 expression is characteristic of repeatedly restimulated effector memory Th cells and thus of the pathogenic memory Th cells of chronic inflammation. Th lymphocytes from the inflamed joint or gut tissue of patients with rheumatic diseases, Crohns disease or ulcerative colitis express high levels of twist1. Expression of twist1 in Th1 lymphocytes limits the expression of the cytokines interferon-, IL-2 and tumor necrosis factor-, and ameliorates Th1-mediated immunopathology in delayed-type hypersensitivity and antigen-induced arthritis. In order to identify the effect of twist1 expression on the function of Th cells, twist1 was ectopically expressed and the transcriptome was compared to empty-virus infected control cells. In addition, this experiment allows for the identification of genes regulated by the transcription factor twist1.
Publication Title
Autoregulation of Th1-mediated inflammation by twist1.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 24 Downloadable Samples
Illumina HiSeq 2500
Description
Somatic hypermutation (SHM) and class switch recombination (CSR) increase the affinity and diversify the effector functions of antibodies during immune responses. Although SHM and CSR are fundamentally different, their independent roles in regulating B cell fate have been difficult to uncouple because a single enzyme, activation-induced cytidine deaminase (encoded by Aicda), initiates both reactions. Here, we used a combination of Aicda and antibody mutant alleles that separate the effects of CSR and SHM on polyclonal immune responses. We found that class-switching to IgG1 biased the fate choice made by B cells, favoring the plasma cell over memory cell fate without significantly affecting clonal expansion in the germinal center (GC). In contrast, SHM reduced the longevity of memory B cells by creating polyreactive specificities that were selected against over time. Our data define the independent contributions of SHM and CSR to the generation and persistence of memory in the antibody system. Overall design: IgG1 and IgM light zone (LZ) and dark zone (DZ) germinal center (GC) B cells were compared in immunized AIDcre/- IgH-96K/+ R26-LSL-YFP mice.
Publication Title
Independent Roles of Switching and Hypermutation in the Development and Persistence of B Lymphocyte Memory.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 20 Downloadable Samples
- Illumina HiSeq 2500
Description
Somatic hypermutation (SHM) and class switch recombination (CSR) increase the affinity and diversify the effector functions of antibodies during immune responses. Although SHM and CSR are fundamentally different, their independent roles in regulating B cell fate have been difficult to uncouple because a single enzyme, activation-induced cytidine deaminase (encoded by Aicda), initiates both reactions. Here, we used a combination of Aicda and antibody mutant alleles that separate the effects of CSR and SHM on polyclonal immune responses. We found that class-switching to IgG1 biased the fate choice made by B cells, favoring the plasma cell over memory cell fate without significantly affecting clonal expansion in the germinal center (GC). In contrast, SHM reduced the longevity of memory B cells by creating polyreactive specificities that were selected against over time. Our data define the independent contributions of SHM and CSR to the generation and persistence of memory in the antibody system. Overall design: IgG1 and IgM light zone (LZ) germinal center (GC) B cells that were Nurr77-GFP+ or Nurr77-GFP- were compared in immunized AIDcre/- IgH-96K/+ Nurr77-GFP mice.
Publication Title
Independent Roles of Switching and Hypermutation in the Development and Persistence of B Lymphocyte Memory.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 2500
Description
The germinal center (GC) is a microanatomical compartment wherein high-affinity antibody-producing B cells are selectively expanded. B cells proliferate and mutate their antibody genes in the dark zone (DZ) of the GC and are then selected by T cells in the light zone (LZ) on the basis of affinity. Here, we show that T cell help regulates the speed of cell cycle phase transitions and DNA replication of GC B cells. Genome sequencing and single-molecule analyses revealed that T cell help shortens S phase by regulating replication fork progression while preserving the relative order of replication origin activation. Thus, high-affinity GC B cells are selected by a mechanism that involves prolonged dwell time in the DZ where selected cells undergo accelerated cell cycles. Overall design: To determine whether GC B cells receiving high levels of T cell help show a specific change in gene expression, we compared DZ cells in the G1 phase of the cell cycle from aDEC-OVA and control aDEC-CS treated GCs using a fluorescent ubiquitination-based cell cycle indicator (Fucci-tg). RNA sequencing revealed that T cell-mediated selection produced an increase in gene expression programs associated with the cell cycle, metabolism, including the metabolism of nucleotides, and genes downstream of c-Myc and the E2F transcription factors.
Publication Title
HUMORAL IMMUNITY. T cell help controls the speed of the cell cycle in germinal center B cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 7 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st), Illumina Genome Analyzer IIx
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Hypoxia increases genome-wide bivalent epigenetic marking by specific gain of H3K27me3.
Sample Metadata Fields
Cell line, Time
View Samples- Mus musculus
- 594 Downloadable Samples
- Affymetrix HT Mouse Genome 430A Array (htmg430a)
Description
We measured the genome-wide expression changes induced by 29 compounds targeting HDACs, DNMTs, histone lysine methyltransferases (HKMTs), and protein arginine methyltransferases (PRMTs) in pancreatic - and -cell lines.
Publication Title
Chromatin-targeting small molecules cause class-specific transcriptional changes in pancreatic endocrine cells.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 22 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Double-stranded microRNA mimics can induce length- and passenger strand-dependent effects in a cell type-specific manner.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Experiment 1 - miR-155 and miR-199 Phenotype
Publication Title
Double-stranded microRNA mimics can induce length- and passenger strand-dependent effects in a cell type-specific manner.
Sample Metadata Fields
Cell line
View Samples