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YTHDF2 suppresses the plasmablast genetic program and promotes germinal center formation

ABSTRACT: YTHDF2 suppresses the plasmablast genetic program and promotes germinal center formation

PROVIDER: PRJNA784593 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR17067013.fastq.gz	Fastqsanger.gz
	SRR17067014.fastq.gz	Fastqsanger.gz
	SRR17067015.fastq.gz	Fastqsanger.gz
	SRR17067016.fastq.gz	Fastqsanger.gz
	SRR17067017.fastq.gz	Fastqsanger.gz

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YTHDF2 suppresses the plasmablast genetic program and promotes germinal center formation

Project description:Antibody-mediated immunity is initiated by B cell interactions with cognate antigen, followed by differentiation into multiple cell subsets, including plasmablast, memory, and germinal center (GC) cells. B cell differentiation trajectories are determined by specific transcription factors, yet very few mechanisms that determine B cell fate at the early stage of the response have been described. Here, we report an epigenetic mechanism that specifically suppresses the plasmablast genetic program and promotes GC B cell fate commitment. Single-cell RNA-seq analysis of antigen-specific B cells revealed activated B cell precursors at the pre-GC stage that express high levels of RNA binding proteins, including YTHDF2, which enhances the decay of methylated transcripts. Ythdf2-deficient B cells exhibited intact proliferation and upregulation of early activation markers in response to antigenic stimulation, whereas differentiation into GC B cells was blocked. Mechanistically, B cells required YTHDF2 to attenuate the plasmablast genetic program during GC seeding, and key transcripts of plasmablast-related genes, including Irf4 and Xbp1, were methylated and bound by YTHDF2. Modulation of YTHDF2-dependent gene expression by YTHDF1 and YTHDF3 was less pronounced, and no functional redundancy of these paralogs in GC seeding was observed. Collectively, this study reveals a novel epigenetic mechanism that specifically directs appropriate B cell fate commitment through post-transcriptional suppression of gene expression.

2022-04-24 | GSE189819 | GEO

Proteome profiling of mouse germinal center B cells

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

Transcriptional profiles of knockouts of m6A writer and readers in Germinal Center B cells

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.

2021-07-21 | GSE180359 | GEO

ChIPseq analyses in germinal center B cells

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.

2015-12-04 | E-GEOD-68349 | biostudies-arrayexpress

ChIPseq analyses in germinal center B cells

2015-12-04 | GSE68349 | GEO

Deletion of miR-15a/16-1 in murine germinal center B-cells.

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.

2021-09-09 | PXD021323 | Pride

The influence of TFEB on gene expression in primary murine germinal center and non-germinal center B cells

Project description:To investigate TFEB-dependent mRNA expression in murine B cells, FACS-sorted germinal center and non-germinal center B lymphocytes of B-cell-specific conditional TFEB KO mice and control littermates were subjected to RNA sequencing analysis

2024-06-25 | GSE237799 | GEO

Gene Expression Profiles of Germinal Center B Cells

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

RNA-seq analysis of gene expression profile in Setd2 WT and KO germinal center B cells and Phf19 WT and KO germinal center B cells

Project description:The goals of this study are to compare gene expression profiles of Setd2 WT and KO germinal center B cells and reveal the underlying mechanisms by which Setd2 regulates germinal center B cell responses. Further our study aims to compare gene expression profiles of Phf19 WT and KO germinal center B cells reveal the underlying mechanisms by which Phf19 regulates germinal center B cells responses. Finally, we combine the two profiles and investigate the relation shape betweeen Setd2 dependent regulation and Phf19 dependent regulation.

2024-09-14 | GSE184075 | GEO

Dynamic Regulation of Tfh Clonal Selection During the Germinal Center Reaction

Project description:The Germinal center is a dynamic microenvironment wherein B cells expressing high affinity antibody variants produced by hypermutation are selected for clonal expansion by limiting numbers of T follicular helper cells. Although a great deal is known about the mechanisms that control B cell selection in the germinal center, far less is understood about the clonal behavior of the T follicular helper cells that regulate this process. Here we report on the dynamic behavior of clones of T follicular helper cells during the germinal center reaction. We find that like germinal center B cells, T follicular helper cells undergo antigen dependent selection during the germinal center reaction resulting in differential proliferative expansion and contraction. Increasing the amount of antigen presented in the germinal center leads to increased T follicular cell division. Competition between T follicular helper cell clones is mediated by T cell receptor affinity for peptide-MHC ligand. Higher affinity T cells expanding preferentially in the germinal center show increased expression of genes downstream of the T cell receptor, genes required for metabolic reprogramming, cell division and cytokine production. These dynamic changes lead to dramatic remodeling of the functional T follicular cell repertoire during the germinal center reaction.

2020-03-19 | GSE147182 | GEO

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