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Extracellular vesicle-microRNA transfer controls germinal center reaction and antibody production

ABSTRACT: Extracellular vesicle-microRNA transfer controls germinal center reaction and antibody production

PROVIDER: PRJNA591861 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR10529627.fastq.gz	Fastqsanger.gz
	SRR10529628.fastq.gz	Fastqsanger.gz
	SRR10529629.fastq.gz	Fastqsanger.gz
	SRR10529630.fastq.gz	Fastqsanger.gz
	SRR10529631.fastq.gz	Fastqsanger.gz

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Extracellular vesicle-microRNA transfer controls germinal center reaction and antibody production

Project description:Intercellular communication orchestrates effective immune responses against disease-causing agents. Extracellular vesicles (EVs) are potent mediators of cell-cell communication. EVs carry bioactive molecules, including microRNAs, which modulate gene expression and function in the recipient cell. Here, we show that formation of cognate primary T-B lymphocyte immune contacts promotes transfer to the B cell of a very restricted set of T cell EV-microRNAs (mmu-miR20a-5p, mmu-miR-25-3p and mmu-miR-155-3p). Transferred EV-microRNAs target key genes that control B cell function, including the pro-apoptotic BIM and the cell-cycle regulator PTEN. EV-microRNAs transferred in T-B cognate interactions also promote survival, proliferation and antibody class switching. Using mouse chimeras with Rab27KO EV-deficient T cells, we demonstrate that small EV transfer is required for the germinal center reaction and antibody production in vivo, revealing a novel mechanism that controls B cell responses through the transfer of EV-microRNAs of T cell origin. These findings provide mechanistic insight on the Griscelli syndrome, associated with a mutation in the Rab27a gene and may shed light on this pathogenesis and other immune-related and inflammatory disorders. This SuperSeries is composed of the SubSeries listed below.

2020-01-20 | GSE141045 | GEO

Transfer of extracellular vesicle-microRNA controls germinal center reaction and antibody production.

Project description:Intercellular communication orchestrates effective immune responses against disease-causing agents. Extracellular vesicles (EVs) are potent mediators of cell-cell communication. EVs carry bioactive molecules, including microRNAs, which modulate gene expression and function in the recipient cell. Here, we show that formation of cognate primary T-B lymphocyte immune contacts promotes transfer of a very restricted set of T-cell EV-microRNAs (mmu-miR20-a-5p, mmu-miR-25-3p, and mmu-miR-155-3p) to the B cell. Transferred EV-microRNAs target key genes that control B-cell function, including pro-apoptotic BIM and the cell cycle regulator PTEN. EV-microRNAs transferred during T-B cognate interactions also promote survival, proliferation, and antibody class switching. Using mouse chimeras with Rab27KO EV-deficient T cells, we demonstrate that the transfer of small EVs is required for germinal center reaction and antibody production in vivo, revealing a mechanism that controls B-cell responses via the transfer of EV-microRNAs of T-cell origin. These findings also provide mechanistic insight into the Griscelli syndrome, associated with a mutation in the Rab27a gene, and might explain antibody defects observed in this pathogenesis and other immune-related and inflammatory disorders.

| S-EPMC7132182 | biostudies-literature

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

Dynamic Regulation of Tfh Clonal Selection During the Germinal Center Reaction

Project description:Dynamic Regulation of Tfh Clonal Selection During the Germinal Center Reaction

| PRJNA613275 | ENA

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

RNA-seq data from nsd2 wt and ko germinal center B cells

Project description:The goal of this study was to invetigate the mechanisms by which nsd2 regulate germinal center reaction by comparing RNA-seq data between nsd2 wt and ko germinal center B cells

2018-12-07 | GSE111755 | GEO

Transcriptome analysis of rhesus monkey germinal vesicle and failed-to-mature oocytes

Project description:Oocyte maturation defects are one contributing factor in unexplained female infertility. Failure of some oocytes to undergo germinal vesicle breakdown or progress to second meiotic metaphase in response to an ovulatory stimulus can limit the number of high quality oocytes available for assisted reproduction. Understanding the molecular mechanisms that underlie oocyte maturation failure may lead to novel methods for increasing the number of high quality oocytes available for assisted reproduction, as well as providing new insight into the basic biology of oocyte maturation. Using RNA sequencing, we compared the transcriptome of rhesus monkey oocytes that failed to mature (FTM) in response to an ovulatory stimulus in vivo to normal germinal vesicle and metaphase II stage oocytes.

2018-09-06 | GSE112533 | GEO

Transcription profiling of mouse, bovine and xenopus germinal vesicle stage oocytes reveals a high degree of conservation among species

Project description:Comparative analysis of bovine, mouse and xenopus oocyte transcript profiles. The results from bovine and xenopus germinal vesicle stage oocytes in this experiment were compared to previously-published microarray data on preimplantation development in the mouse (Carter 2003).

2008-02-01 | E-MEXP-1339 | biostudies-arrayexpress

Activation-induced deaminase is critical for the establishment of DNA methylation patterns prior to the germinal center reaction

Project description:Activation-induced deaminase (AID) initiates antibody diversification in germinal center B cells by deaminating cytosines, leading to somatic hypermutation and class-switch recombination. Loss-of-function mutations in AID lead to hyper-IgM syndrome type 2 (HIGM2), a rare human primary antibody deficiency. AID-mediated deamination has been proposed as leading to active demethylation of 5-methycytosines in the DNA, although evidence both supports and casts doubt on such a role. In this study, using whole-genome bisulfite sequencing of HIGM2 B cells, we investigated direct AID involvement in active DNA demethylation. HIGM2 naïve and memory B cells both display widespread DNA methylation alterations, of which approximately 25% are attributable to active DNA demethylation. For genes that undergo active demethylation that is impaired in HIGM2 individuals, our analysis discards AID involvement. We demonstrate that the widespread alterations in the DNA methylation and expression profiles of HIGM2 naïve B cells result from premature overstimulation of the B-cell receptor prior to the germinal center reaction. Our data support a role for AID in B cell central tolerance in preventing the expansion of autoreactive cell clones, affecting the correct establishment of DNA methylation patterns.

2021-04-13 | GSE172011 | GEO

Bovine cumulus cells transcriptome in relation with oocyte chromatin configuration of the germinal vesicle

Project description:Gene expression analysis in cc from COCs with different chromatin configuration (GV0-3) Bovine cumulus cells (4 biological replicates) were collected and grouped according to the oocyte different chromatin configuration of the germinal vesicle described by Lodde et al. 2007. Four GV stages corresponding to the state of chromatin condensation were used (GV0; GV1; GV2 and GV3). Multiple microarray comparisons were performed. First a reference design (GV0 as a reference) was used for a total of three comparisons (GV0 vs GV1; GV0 vs GV2 and GV0 vs GV3) .

2016-04-04 | E-GEOD-79886 | biostudies-arrayexpress

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