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SRP045422
Mus musculus
155 Downloadable Samples
IlluminaHiSeq2500
Description
This study set out to assay the (polyA+) transcriptomes of single mature (MHCII high) mouse medullary thymic epithelial cells (mTEC). Overall design: Following isolation by FACs, the transcriptomes of single mature mTEC was assayed using the Fluidigm C1 microfluidics platform and Illumina RNA-seq.
Publication Title
Population and single-cell genomics reveal the Aire dependency, relief from Polycomb silencing, and distribution of self-antigen expression in thymic epithelia.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 14 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
This study set out to assay the (polyA+) transcriptomes of specific FACS sorted populations of mouse thymic epithelial cells (TEC). Overall design: Two biological replicates of each of seven murine TEC populations were FACS sorted and sequenced.
Publication Title
Population and single-cell genomics reveal the Aire dependency, relief from Polycomb silencing, and distribution of self-antigen expression in thymic epithelia.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 9 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The liver stages of malaria sporozoites develop in the hepatocyte cytoplasm inside a parasitophorous vacuole (PV). The circumsporozoite (CS) protein, the major surface protein of sporozoites, traverses the PV membrane and enters the cytoplasm and nucleus of hepatocytes. CS export into the cytoplasm requires the presence of pexel/VTS motifs. The transport of CS into the host nucleus is then mediated by importin (Imp) alpha3/beta1 that binds to the nuclear localization signal of CS localized in the conserved region II-plus. The NLSs of CS and of NFkB p50 share the same Imp. The entry of NFkB p50 into the nucleus is strongly inhibited in cell lines expressing CS, and in infected hepatocytes. Micro-array data from CS expressing cell line shows that 40 NFkB targets were significantly down regulated. Among them inflammation related MIP3a and PTGS transcripts were 65 and 22 fold down regulated, thus explaining the notable absence of inflammatory cells surrounding exo-erythrocytic forms (EEFs). The presence of CS in the cytoplasm of hepatocytes enhances EEF growth both in vitro and in vivo. Therefore Plasmodium blood stages and EEFs use the same strategy to secrete proteins into the cytoplasm of host cells and remodel it to the parasites advantage.
Publication Title
Plasmodium circumsporozoite protein promotes the development of the liver stages of the parasite.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus, Homo sapiens
- 15 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Identification of human germinal center light and dark zone cells and their relationship to human B-cell lymphomas.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 7 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Microarrays of gene expression in human germinal center light zone and dark zone B cells sorted according to the expression of cell surface molecules CD83 and CXCR4
Publication Title
Identification of human germinal center light and dark zone cells and their relationship to human B-cell lymphomas.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Microarrays of gene expression in mouse germinal center light zone and dark zone B cells sorted according to the expression of cell surface molecules CD83 and CXCR4
Publication Title
Identification of human germinal center light and dark zone cells and their relationship to human B-cell lymphomas.
Sample Metadata Fields
Specimen part
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
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Germinal centers (GC) arise within B cell follicles upon antigenic challenge. In the dark zones (DZ) of GCs, B cells proliferate and hypermutate their immunoglobulin genes, and mutants with increased affinity are positively selected in the light zone (LZ) to either differentiate into plasma and memory cells, or re-enter the DZ for further refinement. However, the molecular circuits governing GC positive selection are not known. Here, we show that the GC reaction requires the biphasic regulation of c-MYC expression, involving its transient induction during early GC commitment, its repression by BCL6 in DZ B cells, and its re-induction in a subpopulation of positively selected LZ B cells destined to DZ re-entry. Accordingly, acute disruption of MYC function in vivo leads to GC collapse, indicating an essential role in GC physiology. These results have implications for our understanding of GC selection and the role of MYC deregulation in B cell lymphomas.
Publication Title
The proto-oncogene MYC is required for selection in the germinal center and cyclic reentry.
Sample Metadata Fields
Specimen part
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
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