Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA329004 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The transcription factor Bcl6 orchestrates the germinal center reaction through its actions in B and T cells, and regulates inflammatory signaling in macrophages. We report that genetic replacement by mutant Bcl6, which cannot bind corepressors to its BTB domain, disrupted  germinal center formation and immunoglobulin affinity maturation, due to a defect in B cell  proliferation and survival. In contrast, BTB loss of function had no effect on T follicular helper cell differentiation and function, nor other T helper subsets. Bcl6 null mice displayed a lethal inflammatory phenotype, whereas BTB mutant mice experienced normal healthy lives with no inflammation. Bcl6 repression of inflammatory responses in macrophages was accordingly independent of the BTB domain repressor function. Bcl6 thus mediates its actions through lineage-specific biochemical functions. ChIP-seq for Bcl6, SMRT and BCOR in germinal center B cells
2013-03-03 | E-GEOD-43350 | biostudies-arrayexpress
Project description:In immune responses, activated T cells migrate to B cell follicles and develop to T follicular helper (Tfh) cells, a new subset of CD4+ T cells specialized in providing help to B lymphocytes in the induction of germinal centers 1-3. Although Bcl6 has been shown to be essential in Tfh cell function, it may not regulate the initial migration of T cells 4 or the induction of Tfh program as exampled by CXCR5 upregulation 5. Here, we show that the Achaete-Scute homologue 2 (Ascl2) gene that encodes a basic helix-loop-helix (bHLH) transcription factor 6, is selectively upregulated in its expression in Tfh cells. Ectopic expression of Ascl2 uniquely upregulates CXCR5 but not Bcl6 and downregulates CCR7 expression in T cells in vitro and accelerates T cell migration to the follicles and Tfh cell development in vivo. Combined transcriptome profiling and genome-wide occupancy analysis indicate that Ascl2 directly regulates Tfh-related genes while inhibits expression of Th1 and Th17 genes. Acute deletion of Ascl2 as well as blockade of its function with the Id3 protein in peripheral CD4+ T cells results in a failure in Tfh cell development and the germinal center response. Conversely, mutation of Id3, known to cause antibody-mediated autoimmunity, greatly enhances Tfh cell generation. Thus, Ascl2 critically and directly initiates Tfh cell development. Decide Ascl2 binding sites in CD4+ T cells
2014-01-01 | E-GEOD-52839 | biostudies-arrayexpress
Project description:Previous studies have demonstrated that E-proteins induce AID expression in activated B cells. Here we have examined the role of Id3 in germinal center (GC) cells. We found that Id3 expression is high in follicular B-lineage cells but declines in GC cells. Immunized mice depleted for Id3 expression displayed a block in germinal center B cell maturation, showed reduced numbers of marginal zone B cells and class switched cells, were associated with decreased antibody titers and lower numbers of plasma cells. In vitro Id3-depleted B cells displayed a defect in class switch recombination. Whereas AID levels were not altered in Id3-depleted activated B cells, the expression of a subset of genes encoding for signaling components of antigen receptor, cytokine receptor and chemokine receptor mediated signaling was significantly impaired. We propose that during the GC reaction Id3 levels decline to activate the expression of genes encoding for signaling components that mediate B cell receptor and or cytokine-mediated signaling to promote the differentiation of GC B cells.
2016-08-18 | GSE84374 | GEO
Project description:It is now well established that the E- and Id-protein axis regulates multiple steps in lymphocyte development. However, it remains unknown as to how E- and Id-proteins mechanistically enforce and maintain the naïve T cell fate. Here we show that Id2 and Id3 suppressed the development and expansion of innate-variant TFH cells. Innate-variant TFH cells required MHC Class I-like signalling and were associated with germinal center B cell development. We found that Id2 and Id3 induced Foxo1 and Foxp1 expression to antagonize the activation of TFH transcription signature. We show that Id2 and Id3 acted upstream of the Hif1a/Foxo/AKT/mTORC1 pathway as well as the c-myc/p19Arf module to control cellular expansion and activation. We found that mice depleted for Id2 and Id3 expression developed colitis and αβ T cell lymphomas. Lymphomas depleted for Id2 and Id3 expression displayed elevated levels of c-myc whereas p19Arf abundance declined. Transcription signatures of Id2- and Id3-depleted lymphomas revealed similarities with genetic deficiencies associated with Burkitt lymphoma. We propose that in response to antigen receptor and/or cytokine signaling the E-Id protein axis modulates the activities of the PI3K-AKT-mTORC1-Hifa and c-myc/p19Arf pathways to control cellular expansion and homeostatic proliferation. RNA-seq data of 5 of wild type CD4SP cells, 3 of wild type Tfh cells, 3 of Id3-/- CD4SP cells, 3 of Id2-/-Id3-/-(dKO) CD4SP cells, and 6 of Id2-/-Id3-/- lymphoma cells.
2015-03-04 | E-GEOD-64779 | biostudies-arrayexpress
Project description:Dynamic changes in E protein activity orchestrate germinal center and plasma cell development [RNA-Seq]
| PRJNA295176 | ENA
Project description: Not available
| S-EPMC8784167 | biostudies-literature
Project description:Visualizing germinal center B cell dynamics at single cell transcriptome resolution
| PRJNA314939 | ENA
Project description:It is now well established that the E- and Id-protein axis regulates multiple steps in lymphocyte development. However, it remains unknown as to how E- and Id-proteins mechanistically enforce and maintain the naïve T cell fate. Here we show that Id2 and Id3 suppressed the development and expansion of innate-variant TFH cells. Innate-variant TFH cells required MHC Class I-like signalling and were associated with germinal center B cell development. We found that Id2 and Id3 induced Foxo1 and Foxp1 expression to antagonize the activation of TFH transcription signature. We show that Id2 and Id3 acted upstream of the Hif1a/Foxo/AKT/mTORC1 pathway as well as the c-myc/p19Arf module to control cellular expansion and activation. We found that mice depleted for Id2 and Id3 expression developed colitis and αβ T cell lymphomas. Lymphomas depleted for Id2 and Id3 expression displayed elevated levels of c-myc whereas p19Arf abundance declined. Transcription signatures of Id2- and Id3-depleted lymphomas revealed similarities with genetic deficiencies associated with Burkitt lymphoma. We propose that in response to antigen receptor and/or cytokine signaling the E-Id protein axis modulates the activities of the PI3K-AKT-mTORC1-Hifa and c-myc/p19Arf pathways to control cellular expansion and homeostatic proliferation.
2015-03-04 | GSE64779 | GEO
Project description:Essential role of the transcription factors E2A and E2-2 in germinal center B cell and plasma cell development
| PRJNA311335 | ENA
Project description:Signatures of murine B-cell development implicate Yy1 as a regulator of the germinal center-specific program
| PRJNA136867 | ENA