Germinal Center B cell transcriptional profiles in Mef2b mouse models
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ABSTRACT:
PROVIDER: PRJNA434245 | ENA |
REPOSITORIES: ENA
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Project description:The MEF2B transcription factor is recurrently mutated in germinal-center (GC)-derived B-cell lymphomas, but its role in normal and neoplastic GC development is unknown. Here we identify MEF2B transcriptional targets in GC, which indicate its control of cell proliferation, apoptosis, GC confinement and differentiation. Consistently, Mef2b deletion reduces GC formation in mice. The most common tumor-associated MEF2B mutant (MEF2BD83V) is hypomorphic, but escapes binding and negative regulation by Cabin1 and HDACs. Mef2bD83V expression leads to GC enlargement and GC-derived tumors in 25% of the animals. This phenotype becomes fully penetrant in combination with BCL2 de-regulation, an event commonly associated with MEF2B mutations in human lymphoma. These results identify MEF2B as a critical GC regulator, and as a dominant oncogene in lymphomagenesis.
2018-09-10 | GSE110676 | GEO
Project description:We report the gene expression profiles of germinal center B cells obtained by FACS analyses of normal human lymph nodes. We used FACS analyses to isolate germinal center B cells from 3 different individuals with one individual sampled twice. The overall goal was simply to identify genes that are highly expressed or silent in these purified cell populations.
2009-07-31 | E-GEOD-16712 | biostudies-arrayexpress
Project description:We report the gene expression profiles of germinal center B cells obtained by FACS analyses of normal human lymph nodes.
2009-07-31 | GSE16712 | GEO
Project description:Productive B cell responses are critical to protect a host from infection. The spleen and lymph nodes are populated by resting follicular B cells, which can enter germinal centers upon antigen encounter. Once in the germinal center, B cells migrate between the dark and light zones, where they undergo somatic hypermutation and selection, respectively. While germinal center B cells have been studied, an intense molecular understanding of these cells/subsets (and the differences between them) is lacking.
2020-04-06 | PXD015524 | Pride
Project description:The chemokines CXCL13 and CXCL12 are reported to be important for the germinal center reaction. Since CXCL12-deficient mice are embryonically lethal, here we took advantage of the Cxcl13-Cre/TdTomato mouse models to genetically ablate CXCL12 from B cell-interacting reticular cells and examine the molecular consequence on germinal center B cells. Spatial segregation of follicular dendritic cells, germinal center B cells and follicular helper T cells is impaired in Cxcl13-Cre/TdTomato Cxcl12fl/fl mice. Single cell transcriptomic analysis revealed that all germinal center B cell subsets (corresponding to distinct stages of the germinal center response) are present in draining lymph nodes of immunized CXCL12-conditionally deficient mice. While most transcriptional regulators of the germinal center response are unperturbed by the genetic perturbation of CXCL12, Bach2 levels were elevated in germinal center B cells from lymph nodes of Cxcl12fl/fl mice. Moreover, single cell B cell receptor sequencing revealed that germinal center B cells in Cxcl13-Cre/TdTomato Cxcl12fl/fl mice harbour a lower mutational burden when compared to germinal center B cells isolated from immunized control mice. Gene expression profiles were validated by flow cytometry and suggest that the provision of CXCL12 by reticular cells governs efficient germinal center responses.
2020-05-12 | E-MTAB-8454 | biostudies-arrayexpress
Project description:We performed RNA-seq (MARS-seq) on germinal center (GC) light zone and dark zone B cells sorted to purity from freshly dissociated mouse popliteal lymph nodes immunized with NP-KLH for 7 to 14 days. Germinal center B cell subsets were gated as follows: Dump (CD8, CD4, F4/80, Gr-1)- B220+ CD38- GL-7+ FAS+. Dark zone GC cells were in addition CD86lo, CXCR4hi; LZ cells were in addition CD86hi, CXCR4lo. Three different mouse models were used: AID-cre Mettl3-flox, AID-cre Ythdf2-flox, Igf2bp3-knockout. We used these data to derive differentially expressed genes between B cell subsets of control and knockout genotypes. We also performed m6A-IP on ex vivo activated wild type B cells and determined the m6A targets in B cells. These studies revealed that the GC response depends on m6A RNA methylation and the functions of specific methyl-readers Ythdf2 and Igf2bp3.
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Project description:Germinal center B cells were isolated from human tonsil tissue and crosslinked. ChIP was performed on two distinct pools of germinal center cells, each obtained from 3-5 donors. The experiment includes two biological replicates (germinal center cell pools from different donors). ChIP was performed on both pools and subject to library preparation and sequencing. Input DNA was sequenced for both pools.
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Project description:Given the tumor suppressing function of miR-15a/16-1 cluster, we studied its role in the germinal center B-cells that give rise to most lymphoid malignancies.
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Project description:Germinal center B cells were isolated from human tonsil tissue and crosslinked. ChIP was performed on two distinct pools of germinal center cells, each obtained from 3-5 donors.
2015-12-04 | GSE68349 | GEO
Project description:The goals of this study are to compare gene expression profiles of Uhrf1 WT and KO germinal center B cells and reveal the underlying mechanisms by which Uhrf1 regulates germinal center B cell responses. We found that upon Uhrf1 depeletion in germinal center B cells, most of the differentially expressed genes were upreguated.
2018-03-26 | GSE102270 | GEO