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

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

PROVIDER: PRJNA445965 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR6907700_1.fastq.gz	Fastqsanger.gz
	SRR6907700_2.fastq.gz	Fastqsanger.gz
	SRR6907701_1.fastq.gz	Fastqsanger.gz
	SRR6907701_2.fastq.gz	Fastqsanger.gz
	SRR6907702_1.fastq.gz	Fastqsanger.gz

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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.

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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.

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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.

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

Project description:RNAseq on B cells from HSC to GC B cell in mouse

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NGFR regulates germinal center B-cell activation and negative selection

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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.

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Dynamic Regulation of Tfh Clonal Selection During the Germinal Center Reaction

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Coupled analysis of transcriptional states and somatic hypermutation in germinal center B cells reveals role for oxidative phosphorylation in positive selection

Project description:In this work we illustrate the power of coupling single cell analysis of transcriptional states with somatic hypermutation of germinal center B cells to reveal unanticipated roles of metabolic programs in the positive selection. We use massively parallel 5'-end scRNA-seq to simultaneously capture transcriptome states and mutation profiles of IgH variable genes in individual cells. Our computational analyses reveal that the OXPHOS module is enhanced in GC B cells undergoing positive selection in response to different antigens. Through deleting the Cox10 gene, which encodes a cytochrome oxidase assembly factor, specifically in GC B cells, we demonstrate that OXPHOS activity is required for cell division and positive selection. Furthermore, we show that chemical augmentation of OXPHOS activity facilitates the positive selection of GC B cells in vivo. Our findings therefore reveal that tuning of OXPHOS activity by increased affinity BCRs is critical for clonal expansion and positive selection.

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PRMT1 is required for antibody affinity maturation by preventing premature B cell differentiation

Project description:Germinal center (GC) B cells undergo cycles of somatic hypermutation and selection, thus increasing their antibody affinity before differentiating into plasma or memory cells. The mechanisms dictating the dynamics of GC B cells are incompletely understood. We show that ablating the Protein arginine methyltransferase 1 (PRMT1) in GC B cells reduces antibody affinity maturation by impairing GC dynamics, as shown by compromised GC expansion, accumulation of CXCR4- B cells, and increased memory B cell differentiation, partly, at the expense of plasma cell production. Furthermore, PRMT1 distinguishes the subset of GC B cells that reenter the GC dark zone after positive selection, in which it is upregulated by Myc in conjunction with mTORC signaling. PRMT1 opposes mature B cell differentiation, as shown by higher plasma cell differentiation of PRMT1-deficient B cells activated ex vivo, a function co-opted by B cell lymphoma cells, in which PRMT1 expression also correlates with Myc expression and outcome.

2023-04-27 | GSE189276 | GEO

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

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