Homo sapiens
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: E-GEOD-58365
PROVIDER: PRJNA252112 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:T Follicular helper (Tfh) cell is an effector CD4+ T cell subset specialized in helping B cells in germinal centers (GC) reactions. Although Bcl6 was identified as a Tfh-specific transcription factor essential for their development, the molecular mechanisms underlying Bcl6 regulation and Tfh cell commitment remain unclear. Here, we report that Tox2 transcription factor is highly expressed in Tfh cells, regulated by Bcl6 and STAT3. Forced expression of Tox2 drives Bcl6 expression and Tfh development. Mechanistically, Tox2 directly binds to Tfh-associated genes, including Bcl6, and functions to promote their chromatin accessibility and modulate the activities of other Tfh-regulating factors. Conversely, genetic deletion of Tox2 results in defective Tfh differentiation, and inhibiting both Tox and Tox2 in T cells abolishes Tfh differentiation and GC response. Thus, our results demonstrate that Tox2 is a key transcription factor that regulates Bcl6 expression and Tfh development and suggest a Tox2-Bcl6 axis in feed-forward regulation of Tfh program.
2019-10-30 | GSE136539 | GEO
Project description:T Follicular helper (Tfh) cell is an effector CD4+ T cell subset specialized in helping B cells in germinal centers (GC) reactions. Although Bcl6 was identified as a Tfh-specific transcription factor essential for their development, the molecular mechanisms underlying Bcl6 regulation and Tfh cell commitment remain unclear. Here, we report that Tox2 transcription factor is highly expressed in Tfh cells, regulated by Bcl6 and STAT3. Forced expression of Tox2 drives Bcl6 expression and Tfh development. Mechanistically, Tox2 directly binds to Tfh-associated genes, including Bcl6, and functions to promote their chromatin accessibility and modulate the activities of other Tfh-regulating factors. Conversely, genetic deletion of Tox2 results in defective Tfh differentiation, and inhibiting both Tox and Tox2 in T cells abolishes Tfh differentiation and GC response. Thus, our results demonstrate that Tox2 is a key transcription factor that regulates Bcl6 expression and Tfh development and suggest a Tox2-Bcl6 axis in feed-forward regulation of Tfh program.
2019-10-30 | GSE136538 | GEO
Project description:T Follicular helper (Tfh) cell is an effector CD4+ T cell subset specialized in helping B cells in germinal centers (GC) reactions. Although Bcl6 was identified as a Tfh-specific transcription factor essential for their development, the molecular mechanisms underlying Bcl6 regulation and Tfh cell commitment remain unclear. Here, we report that Tox2 transcription factor is highly expressed in Tfh cells, regulated by Bcl6 and STAT3. Forced expression of Tox2 drives Bcl6 expression and Tfh development. Mechanistically, Tox2 directly binds to Tfh-associated genes, including Bcl6, and functions to promote their chromatin accessibility and modulate the activities of other Tfh-regulating factors. Conversely, genetic deletion of Tox2 results in defective Tfh differentiation, and inhibiting both Tox and Tox2 in T cells abolishes Tfh differentiation and GC response. Thus, our results demonstrate that Tox2 is a key transcription factor that regulates Bcl6 expression and Tfh development and suggest a Tox2-Bcl6 axis in feed-forward regulation of Tfh program.
2019-10-30 | GSE136537 | GEO
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:Upon immunization with a T cell dependent antigen naive follicular B cells (Fo) are activated and a germinal center reaction is induced. Within the next 2 weeks large germinal centers develop where the process of affinity maturation takes place. To analyze the gene expression profile of resting and activated B cells, follicular B cells (Fo), B cells from early (GC1) and late germinal centers (GC2) were isolated and their gene expression profile compared.
2011-03-29 | GSE28237 | GEO
Project description:Our data demonstrated that Bcl6 directly binds and represses trafficking receptors S1pr1 and Grp183 by recruiting Hdac2 through the RD2 domain. Deregulation of these genes impairs B-cell migration and may contribute to the Germinal Center failure in Bcl6RD2MUT mice. RNAseq was performed in endogenous BCL6-depleted OCI-LY1 cells rescued with either WT or RD mutant BCL6 (N=3 for each group).
2014-09-14 | E-GEOD-58365 | biostudies-arrayexpress
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.
2013-03-03 | GSE43350 | GEO
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:In response to T cell-dependent antigens, mature B cells are stimulated to form germinal centers, which are the place of B cell affinity maturation and selection. Here, we dissected the heterogeneity of germinal center B cells and reconstructed their pathway of differentiation using single-cell transcriptomic analysis.
2020-06-17 | GSE139891 | GEO
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 gene expression patterns of CD4+ T cells with overexpressed Ascl2 or Tfh cells
2014-01-01 | E-GEOD-52838 | biostudies-arrayexpress