IL-21 Shapes the B Cell Response in a Context-Dependent Manner [RNA-seq
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1180891 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR31190019_1.fastq.gz | Fastqsanger.gz | |||
| SRR31190019_2.fastq.gz | Fastqsanger.gz | |||
| SRR31190020_1.fastq.gz | Fastqsanger.gz | |||
| SRR31190020_2.fastq.gz | Fastqsanger.gz | |||
| SRR31190021_1.fastq.gz | Fastqsanger.gz |
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Similar Datasets
Project description:IL-21 Shapes the B Cell Response in a Context-Dependent Manner [CUT&RUN]
| PRJNA1180890 | ENA
Project description:The cytokine interleukin-21 (IL-21) is a pivotal T cell-derived signal crucial for germinal center (GC) responses, but the precise mechanisms by which IL-21 influences B cell function remain elusive. Here, we investigated the B cell-intrinsic role of IL-21 signaling by employing a novel IL-21 receptor (Il21r) conditional knock-out mouse model and ex vivo culture systems and uncovered a surprising duality of IL-21 signaling in B cells. While IL-21 stimulation of naïve B cells led to Bim-dependent apoptosis, it promoted robust proliferation of pre-activated B cells, particularly class-switched IgG1+ B cells ex vivo. Consistent with this, B cell-specific deletion of Il21r led to a severe defect in IgG1 responses in vivo following immunization. Intriguingly, Il21r-deleted B cells are significantly impaired in their ability to transition from a pre-GC to a GC state following immunization. Although Il21r-deficiency did not affect the proportion of IgG1+ B cells among GC B cells, it greatly diminished the proportion of IgG1+ B cells among the plasmablast/plasma cell population. Collectively, our data suggest that IL-21 serves as a critical regulator of B cell fates, influencing B cell apoptosis and proliferation in a context-dependent manner.
2025-01-01 | GSE280838 | GEO
Project description:The cytokine interleukin-21 (IL-21) is a pivotal T cell-derived signal crucial for germinal center (GC) responses, but the precise mechanisms by which IL-21 influences B cell function remain elusive. Here, we investigated the B cell-intrinsic role of IL-21 signaling by employing a novel IL-21 receptor (Il21r) conditional knock-out mouse model and ex vivo culture systems and uncovered a surprising duality of IL-21 signaling in B cells. While IL-21 stimulation of naïve B cells led to Bim-dependent apoptosis, it promoted robust proliferation of pre-activated B cells, particularly class-switched IgG1+ B cells ex vivo. Consistent with this, B cell-specific deletion of Il21r led to a severe defect in IgG1 responses in vivo following immunization. Intriguingly, Il21r-deleted B cells are significantly impaired in their ability to transition from a pre-GC to a GC state following immunization. Although Il21r-deficiency did not affect the proportion of IgG1+ B cells among GC B cells, it greatly diminished the proportion of IgG1+ B cells among the plasmablast/plasma cell population. Collectively, our data suggest that IL-21 serves as a critical regulator of B cell fates, influencing B cell apoptosis and proliferation in a context-dependent manner.
2025-01-01 | GSE280837 | GEO
Project description:IL-21 induces B cell activation, and differentiation into antibody-secreting plasmablasts in vitro. This process is abolished by loss-of function mutations in STAT3 We used microarrays to identify genes that are induced by IL-21 in a STAT3-dependent manner
2014-01-09 | GSE51587 | GEO
Project description:IL-21 induces B cell activation, and differentiation into antibody-secreting plasmablasts in vitro. This process is abolished by loss-of function mutations in STAT3 We used microarrays to identify genes that are induced by IL-21 in a STAT3-dependent manner Sort-purified naïve B cells from four healthy donors and three patients with AD-HIES due to heterozygous STAT3 mutations were cultured for four days with CD40L in the presence or absence of IL-21 (50ng/ml). After four days, RNA was extracted from the harvested cells and the genetic profile was analysed by microarray.
2014-01-09 | E-GEOD-51587 | biostudies-arrayexpress
Project description:The canonical pathway for IL-1β production requires TLR-mediated NF-κB-dependent Il1b gene induction, followed by caspase-containing inflammasome-mediated processing of pro-IL-1β. Here we show that IL-21 unexpectedly induces IL-1β production in conventional dendritic cells (cDCs) via a STAT3-dependent but NF-κB-independent pathway. IL-21 does not induce Il1b expression in CD4+ T cells, with differential histone marks present in these cells versus cDCs. IL-21-induced IL-1β processing in cDCs does not require caspase-1 or caspase-8 but depends on IL-21-mediated death and activation of serine protease(s). Moreover, STAT3-dependent IL-1β expression in cDCs at least partially explains the IL-21-mediated pathologic response occurring during infection with Pneumonia Virus of Mice. These results demonstrate lineage-restricted IL-21-induced IL-1β via a non-canonical pathway and provide evidence for its importance in vivo.
2015-07-07 | GSE61677 | GEO
Project description:In this study we compared the effects of IL-2, IL-15, and IL-21 on the gene expression, activation of cell signaling pathways, and functional properties of cells derived from the CD4+ cutaneous T-cell lymphoma (CTCL). Whereas both IL-2 and IL-15 that signal through receptors that share the common gamma chain and the beta chain modulated the expression of >1,000 genes, IL-21 that signals via the receptor also containing gamma chain up-regulated <40 genes. All three cytokines induced tyrosine phosphorylation of Jak1 and Jak3. However, only IL-2 and IL-15 strongly activated STAT5, PI3K/Akt, and MEK/ERK signaling pathways. In contrast, IL-21 selectively activated STAT3. Whereas all three cytokines protected CTCL cells from apoptosis, only IL-2 and IL-15 promoted their proliferation. The effects of the cytokine stimulation were Jak3- and Jak1-kinase dependent. These findings document the vastly different impact of IL-2 and IL-15 vs. IL-21 on malignant CD4+ T cells. They also suggest two novel therapeutic approaches to CTCL and, possibly, other CD4+ T cell lymphomas: inhibition of the Jak1/Jak3 kinase complex and, given the known strong immunostimulatory properties of IL-21 on CD8+ T, NK, and B cells, application of this cytokine to boost an immune response against malignant CD4+ T cells. Keywords: 3 replicates in each of 4 conditions
2008-02-19 | GSE8685 | GEO
Project description:murine naive CD8+ T-cell samples for control or treated with 100ng/ml of IL-15 and/or IL-21 for 4 hours Keywords: other
2004-12-11 | GSE2059 | GEO
Project description:T-Box Expressed in T cells (TBET) and CD11c expression in B cells is linked with IgG2c isotype switching, virus-specific immune responses, and humoral autoimmunity. However, the activation requisites and regulatory cues governing TBET and CD11c expression remain poorly defined. In this article, we reveal a relationship among TLR engagement, IL-4, IL-21, and IFN-g that regulates TBET expression in B cells. We find that IL-21 or IFN-g directly promote TBET+ expression in the context of TLR engagement. Further, IL-4 antagonizes TBET induction. Finally, IL-21, but not IFN-g, promotes CD11c expression independent of TBET. Using influenza virus and Heligmosomoides polygyrus infections, we show that these interactions function in vivo to determine whether TBET+ and CD11c+ B cells are formed. These findings suggest that TBET+ B cells seen in health and disease share the common initiating features of TLR-driven activation within this circumscribed cytokine milieu.
2016-01-23 | GSE77145 | GEO
Project description:The canonical pathway for IL-1? production requires TLR-mediated NF-?B-dependent Il1b gene induction, followed by caspase-containing inflammasome-mediated processing of pro-IL-1?. Here we show that IL-21 unexpectedly induces IL-1? production in conventional dendritic cells (cDCs) via a STAT3-dependent but NF-?B-independent pathway. IL-21 does not induce Il1b expression in CD4+ T cells, with differential histone marks present in these cells versus cDCs. IL-21-induced IL-1? processing in cDCs does not require caspase-1 or caspase-8 but depends on IL-21-mediated death and activation of serine protease(s). Moreover, STAT3-dependent IL-1? expression in cDCs at least partially explains the IL-21-mediated pathologic response occurring during infection with Pneumonia Virus of Mice. These results demonstrate lineage-restricted IL-21-induced IL-1? via a non-canonical pathway and provide evidence for its importance in vivo. Genome-wide transcription factors mapping and binding of STAT3, H3K4me3, H3K27me, H3K4me1, H3K27ac in mouse CD4+ T cells and dendritic cells in WT and Stat3-/- mice. RNA-Seq is performed in mouse CD4+ T cells and dendritic cells in WT mice, with or without indicated cytokines.
2015-07-07 | E-GEOD-61677 | biostudies-arrayexpress