Dynamic changes in E protein activity orchestrate germinal center and plasma cell development
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Wei Shi
PROVIDER: E-GEOD-72832 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Humoral immunity requires the generation of high-affinity antibodies, which involves the generation of germinal centres (GC) promoting class switch and affinity maturation of antigen-specific B cells, and the differentiation of long-lived plasma cells. This multi-layered process is tightly controlled by the activity of a transcriptional network including Bcl6, essential for the development of GC, and Blimp1, required for the differentiation of plasma cells. Here, we reveal an additional layer of complexity by demonstrating that dynamic changes in E-protein activity mediated by Id3 govern both GC and plasma cell differentiation. We show that down-regulation of Id3 expression in B cells in essential for releasing E2A and E2-2, the combined activity of which is required for both GC B cell and plasma cell differentiation. We demonstrate that this pathway controls the expression of multiple key factors required for antigen-induced B cell differentiation, including Blimp1, Xbp1, Mef2b and CXCR4 and is therefore critical for establishing the transcriptional network that controls GC B cell and plasma cell differentiation. Genome binding of transcription factor E2A
2016-05-13 | E-GEOD-72828 | biostudies-arrayexpress
Project description:Humoral immunity requires the generation of high-affinity antibodies, which involves the generation of germinal centres (GC) promoting class switch and affinity maturation of antigen-specific B cells, and the differentiation of long-lived plasma cells. This multi-layered process is tightly controlled by the activity of a transcriptional network including Bcl6, essential for the development of GC, and Blimp1, required for the differentiation of plasma cells. Here, we reveal an additional layer of complexity by demonstrating that dynamic changes in E-protein activity mediated by Id3 govern both GC and plasma cell differentiation. We show that down-regulation of Id3 expression in B cells in essential for releasing E2A and E2-2, the combined activity of which is required for both GC B cell and plasma cell differentiation. We demonstrate that this pathway controls the expression of multiple key factors required for antigen-induced B cell differentiation, including Blimp1, Xbp1, Mef2b and CXCR4 and is therefore critical for establishing the transcriptional network that controls GC B cell and plasma cell differentiation. Transcriptional profiling of wild type, Id3 knockout and E2A/E22 double knockout B cells using RNA sequencing
2016-05-13 | E-GEOD-72831 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE23169: Transcriptional profiling of Ramos germinal center B cells GSE23170: ChIP-on-chip experiment from Ramos cells to analyze genome-wide CRTC2 binding sites in germinal center B cells Refer to individual Series
2012-01-01 | E-GEOD-23171 | biostudies-arrayexpress
Project description:Transcriptional profiling of Ramos germinal center B cells, comparing untreated cells to cells treated with etoposide, and untreated cells to cells treated with anti-IgM. Both treatments, engagement of the B-cell receptor with anti-IgM and induction of DNA double-strand breaks with etoposide, result in phosphorylation and cytoplasmic sequestration of CRTC2, and cause downregulation of known CRTC2 target gene TCL1. The goal of these experiments was to determine what other genes are downregulated by both of these CRTC2-inactivating treatments, and to compare this list to the list of genes whose promoters were occupied by CRTC2 in our ChIP-on-chip assay. Untreated samples vs. etoposide-treated samples, untreated samples vs. anti-IgM-treated samples. Each comparison was done in biological triplicate plus dye swap.
2012-01-01 | E-GEOD-23169 | biostudies-arrayexpress
Project description:The generation of high-affinity antibodies requires germinal center (GC) development and differentiation of long-lived plasma cells in a multilayered process that is tightly controlled by the activity of multiple transcription factors. Here, we reveal a new layer of complexity by demonstrating that dynamic changes in Id3 and E-protein activity govern both GC and plasma cell differentiation. We show that down-regulation of Id3 in B cells is essential for releasing E2A and E2-2, which in a redundant manner are required for antigen-induced B cell differentiation. We demonstrate that this pathway controls the expression of multiple key factors, including Blimp1, Xbp1, and CXCR4, and is therefore critical for establishing the transcriptional network that controls GC B cell and plasma cell differentiation.
| S-EPMC4886367 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2016-05-12 | GSE72832 | GEO
Project description:Humoral immunity requires the generation of high-affinity antibodies, which involves the generation of germinal centres (GC) promoting class switch and affinity maturation of antigen-specific B cells, and the differentiation of long-lived plasma cells. This multi-layered process is tightly controlled by the activity of a transcriptional network including Bcl6, essential for the development of GC, and Blimp1, required for the differentiation of plasma cells. Here, we reveal an additional layer of complexity by demonstrating that dynamic changes in E-protein activity mediated by Id3 govern both GC and plasma cell differentiation. We show that down-regulation of Id3 expression in B cells in essential for releasing E2A and E2-2, the combined activity of which is required for both GC B cell and plasma cell differentiation. We demonstrate that this pathway controls the expression of multiple key factors required for antigen-induced B cell differentiation, including Blimp1, Xbp1, Mef2b and CXCR4 and is therefore critical for establishing the transcriptional network that controls GC B cell and plasma cell differentiation.
2016-05-13 | GSE72831 | GEO
Project description:Humoral immunity requires the generation of high-affinity antibodies, which involves the generation of germinal centres (GC) promoting class switch and affinity maturation of antigen-specific B cells, and the differentiation of long-lived plasma cells. This multi-layered process is tightly controlled by the activity of a transcriptional network including Bcl6, essential for the development of GC, and Blimp1, required for the differentiation of plasma cells. Here, we reveal an additional layer of complexity by demonstrating that dynamic changes in E-protein activity mediated by Id3 govern both GC and plasma cell differentiation. We show that down-regulation of Id3 expression in B cells in essential for releasing E2A and E2-2, the combined activity of which is required for both GC B cell and plasma cell differentiation. We demonstrate that this pathway controls the expression of multiple key factors required for antigen-induced B cell differentiation, including Blimp1, Xbp1, Mef2b and CXCR4 and is therefore critical for establishing the transcriptional network that controls GC B cell and plasma cell differentiation.
2016-05-13 | GSE72828 | GEO
Project description:Higher- or lower-affinity GC B cells are directed to plasma cell or recycling GC cell fates; however, how commitment to the plasma cell fate takes place is unclear. By using the level of Bcl6 as a marker, we found that a population of light zone (LZ) GC cells, Bcl6loCD69hi with IRF4 and higher-affinity BCRs or Bcl6hiCD69hi with lower- affinity BCRs, favored the plasma cell or recycling GC cell fate, respectively. Mechanistically, CD40 acted as a dose-dependent regulator for Bcl6loCD69hi cell formation. Furthermore, we found that ICAM1 and SLAM levels on Bcl6loCD69hi cells were higher than on Bcl6hiCD69hi cells, thereby affording more stable TFH-GC B cell contacts, while attenuating this contact down-regulated IRF4. These data support the model that commitment to the plasma cell begins in the GC, and suggest that stability and possibly duration of TFH-GC B cell contacts are key for formation of plasma cell-prone precursor GC cells.
2018-03-29 | GSE109732 | GEO
Project description:ChIP-on-chip experiment from Ramos cells to analyze genome-wide CRTC2 binding sites in germinal center B cells. The goal was to combine information from our ChIP-on-chip and expression array analyses to compile a list of CRTC2 target genes. CRTC2 was immunoprecipitated from sheared chromatin isolated from untreated Ramos cells using 2 antibodies which recognize distinct epitopes on the CRTC2 protein. Immunoprecipitates were compared to total input chromatin. 2 biological replicates were performed for each antibody.
2012-01-01 | E-GEOD-23170 | biostudies-arrayexpress