Genome wide analysis of germinal center MYC positive B-cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Dinis Calado
PROVIDER: E-GEOD-39443 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Analysis of the gene expression profile between MYC positive and MYC negative germinal center B-cells.
2012-09-11 | GSE39443 | GEO
Project 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. We used microarrays to determine the global gene expression programs that distinguish MYC+ GC B cells from their MYC- negative counterparts.
2012-09-24 | GSE38304 | GEO
Project 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. We used microarrays to determine the global gene expression programs that distinguish MYC+ GC B cells from their MYC- negative counterparts. GFPMYC+ and GFPMYC- GC B cell subpopulations were collected by Fluorescence Activated Cell Sorting (FACS) from B cell enriched fractions of splenic mononuclear cell pools of GFPMYC knock-in mice (12 days after SRBC immunization). 5-20ng of total RNA (RIN>9) for each sample was used as a template for linear cDNA amplification (Ovation RNA amplification Kit, NuGen). cDNA was labeled using the Encore Biotin Labeling Kit (NuGen) and hybridized to Affymetrix Mouse 430.2 gene expression arrays.
2012-09-24 | E-GEOD-38304 | biostudies-arrayexpress
Project description:Characterisation of the splenic light zone germinal center B cells in mice carrying WT endogenous mouse allele and mice carrying a mouse allele (Myc V394D) unable to bind its partner transcription factor Miz1 (Zbtb17). Characterisation of Myc WT memory B cells.
2020-05-08 | GSE129262 | GEO
Project description:MYC-MIZ1 protein interaction in germinal center.
| PRJNA530681 | ENA
Project description:CD34+ hematopoietic stem/progenitor cells were isolated from human cord blood and amplified in vitro for 10-14 days in serum-free medium with specific cytokines (Ju et al., Eur. J. Cell Biol. 82, 75-86, 2003; Hacker et al., Nat. Immunol. 4, 380-386, 2003). Cells were then treated with TGF-beta1 for various periods of time (2, 4, 16 hours) and RNA was prepared and subjected to microarray analysis. Keywords: Response to cytokine treatment for various periods of time.
2006-06-29 | GSE5150 | GEO
Project description:Targeting the PI3K-AKT-mTOR pathway is a promising therapeutic strategy for breast cancer treatment. However, low response rates and the development of acquired resistance to PI3K-AKT-mTOR inhibitors remain major challenges for successful patient treatment. Here, we show that MYC activation is a central and clinically relevant mechanism of resistance to mTOR inhibitors (mTORi) in breast cancer. Multi-omic profiling of mouse invasive lobular carcinoma (ILC) tumors revealed recurrent focal Myc amplification in tumors that acquire resistance to the mTORi AZD8055. The gained MYC activity was significantly associated with biological processes linked to mTORi response. Specifically, MYC counteracted the translation inhibitory effect induced by mTORi by promoting the translation of ribosomal proteins. In vitro and in vivo induction of MYC conferred resistance to AZD8055 as well as the clinically approved mTORi everolimus, both in mouse models of ILC and human breast cancer models. Conversely, AZD8055-resistant ILC cells depended on MYC, as demonstrated by synergistic growth inhibition using mTORi and MYCi combination treatment. Notably, MYC status was significantly associated with poor response to everolimus therapy in metastatic breast cancer patients. Thus, MYC is a clinically relevant determinant of mTORi resistance that may guide the selection of breast cancer patients for mTOR targeted therapies.
2023-05-02 | PXD041927 | Pride
Project description:Background: Germinal center B-cell (GCB) lymphomas are common in children and adults. The prognosis strongly depends on age. Subgroups of GCB-lymphomas are characterized by chromosomal translocations affecting immunoglobulin (IG) loci leading to oncogene deregulation. Methods: Novel IG translocation partners were cloned within the network “Molecular Mechanisms in Malignant Lymphomas” (MMML) by long-distance inverse polymerase chain reaction. Mature aggressive B-cell lymphomas from the MMML as well as pediatric and adult lymphoma trials were analyzed by fluorescence in situ hybridization (FISH) and immunhistochemistry. Data from 438 MMML cases characterized by gene expression profiling were mined. Results: Cloning of unknown IG partners identified a t(6;14)(p25;q32) juxtaposing the IRF4 oncogene with the IGH-locus as novel recurrent aberration in GCB lymphoma. FISH analyses of 427 mature B-cell lymphomas for IRF4 translocations revealed 20 IG/IRF4 positive lymphomas (17 IGH/IRF4, 2 IGL/IRF4, 1 IGΚ/IRF4). IG/IRF4-positive lymphomas were predominantly GCB-type diffuse large B-cell lymphomas (DLBCL) or follicular lymphoma grade 3, shared overexpression of IRF4/MUM1 and BCL6 and lacked PRDM1/BLIMP1 expression and t(14;18)/BCL2 breaks. BCL6 aberrations were common. The gene expression profile of IG/IRF4-positive lymphomas was different from other subtypes of DLBCL and a classifier for IG/IRF4 positivity containing 27 genes allowed prediction of 3 additional MMML IG/IRF4-positive cases subsequently proven by FISH. IG/IRF4-positivity was associated with a favorable outcome likely due to significant enrichment of IG/IRF4-positive lymphomas in childhood and young adulthood. Conclusions: Our results suggest IRF4 translocations to be primary genetic alterations in a novel molecularly defined subset of GC-derived lymphomas predominantly affecting children. 271 diffuse large B-Cell lymphoma samples were hybridized to HGU133A Affymetrix GeneChips.
2011-06-24 | E-GEOD-22470 | biostudies-arrayexpress
Project description:We used RNA sequencing to characterize gene expression of Ly75+/+ B1-8hi and Ly75-/- B1-8hi B cells from the germinal center light zone (LZ) 12 h after forcing positive selection of the Ly75+/+ population with anti-DEC205-OVA.
2017-05-25 | GSE98778 | GEO
Project description:Siglec-E is a member of Siglec family of glycan recognition proteins involved in the regulation of myeloid cell activities. Siglec-E preferentially recognizes disialic acid, a glycan epitope consisting of two sialic acids conjugated in alpha2-8 linkage (Zhang JQ et al., Eur J Immunol. 2004, 34:1175-84). BCL-1, a mouse B cell line, expresses disialic acid epitope (Wang SH et al., Glycobiology. 2013, 23:677-89). In this experiment, we attempted at identifying the ligands of Siglec-E on BCL-1 by applying the proximity labeling method we developed (Chang L et al., J Proteome Res. 2017, 16:3929-41).
2022-02-25 | PXD013032 | Pride