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NGFR regulates germinal center B-cell activation and negative selection

ABSTRACT: NGFR regulates germinal center B-cell activation and negative selection

PROVIDER: PRJNA991508 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR25146173.fastq.gz	Fastqsanger.gz
	SRR25146174.fastq.gz	Fastqsanger.gz
	SRR25146175.fastq.gz	Fastqsanger.gz
	SRR25146176.fastq.gz	Fastqsanger.gz
	SRR25146177.fastq.gz	Fastqsanger.gz

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NGFR regulates germinal center B-cell activation and negative selection

Project description:The expression of the Nerve growth factor receptor (NGFR) was described in follicular dendritic cells (FDCs), the major lymphoid stromal cell (LSC) compartment regulating B-cell activation within germinal centers (GCs). However, the role of NGFR in humoral response is not well defined. In this work, we have studied the effect of Ngfr KO in LNs organization and function. Ngfr KO led to spontaneous GC formation and expansion of GC B-cell compartment that were related on Ngfr depletion in non-hematopoietic radioresistant compartment. In agreement, Ngfr KO mice showed alterations in LSC with an increased frequency of FDCs harboring an activated phenotype characterized by the overexpression of CD21/35, MAdCAM-1, and VCAM-1. Moreover, Ngfr KO mice showed GC ectopic location, loss of polarization, impaired high-affinity antibody production, and increased circulating autoantibodies. In addition, Ngfr KO/Bcl2 Tg mice displayed increased levels of autoantibodies, higher incidence of autoimmunity, and decreased overall survival. Our work shows that NGFR maintains GC structure and functionality being involved in the regulation of antibody production and immune tolerance.

2023-12-13 | GSE236511 | 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

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

Signatures of positive selection in germinal center B cells

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

Role of affinity in plasma cell development in the germinal center light zone

Project description:Protective immune responses to many pathogens depend on the development of high affinity antibody-producing plasma cells in germinal centers. Transgenic models suggest that there is a stringent affinity-based barrier to plasma cell development. Whether a similar high affinity barrier regulates plasma cell development under physiologic circumstances, and the nature of the plasma cell fate decision has not been defined precisely. Here we use a fate mapping approach to examine the relationship between germinal center (GC) B cells selected to undergo additional rounds of affinity maturation, germinal center pre-plasma cells and plasma cells. The data show that initial plasma cell selection overlaps with germinal center B cell selection, but that the plasma cell compartment accumulates a less diverse and higher affinity collection of antibodies over time. Thus, whereas the GC continues to diversify over time, affinity-based pre-plasma cell selection sieves the germinal center to enable accumulation of a more restricted group of high affinity antibody secreting plasma cells.

2023-11-02 | GSE246382 | 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

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Genome wide analysis of germinal center MYC positive B-cells

Project description:Analysis of the gene expression profile between MYC positive and MYC negative germinal center B-cells.

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Single-cell transcriptomic analysis of human germinal center B cells

Project description:In response to T cell-dependent antigens, mature B cells are stimulated to form germinal centers, which are the place of B cell affinity maturation and selection. Here, we dissected the heterogeneity of germinal center B cells and reconstructed their pathway of differentiation using single-cell transcriptomic analysis.

2020-06-17 | GSE139891 | GEO

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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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PRMT1 regulates B cell fate after positive selection in the germinal center

Project description:PRMT1 regulates B cell fate after positive selection in the germinal center

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