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Lack of affinity signature for germinal center cells that have initiated plasma cell differentiation (Figure4)

ABSTRACT: Lack of affinity signature for germinal center cells that have initiated plasma cell differentiation (Figure4)

PROVIDER: PRJNA1043113 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR26890931_1.fastq.gz	Fastqsanger.gz
	SRR26890931_2.fastq.gz	Fastqsanger.gz
	SRR26890932_1.fastq.gz	Fastqsanger.gz
	SRR26890932_2.fastq.gz	Fastqsanger.gz
	SRR26890933_1.fastq.gz	Fastqsanger.gz

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Lack of affinity signature for germinal center cells that have initiated plasma cell differentiation

Project description:Lack of affinity signature for germinal center cells that have initiated plasma cell differentiation

| PRJNA1043626 | ENA

Lack of affinity signature for germinal center cells that have initiated plasma cell differentiation (Figure2)

Project description:Lack of affinity signature for germinal center cells that have initiated plasma cell differentiation (Figure2)

| PRJNA944714 | ENA

Lack of affinity signature for germinal center cells that have initiated plasma cell differentiation (Figure4)

Project description:Long-lived plasma cells (PCs) secrete antibodies that can provide sustained immunity against infection. It has been proposed that high affinity cells are preferentially selected into this compartment, potentiating the immune response. We used single cell RNA-seq to track the germinal center (GC) development of Ighg2A10 cells, specific for the Plasmodium falciparum circumsporozoite protein (PfCSP). Following immunization with Plasmodium sporozoites we identified 3 populations of cells in the GC light zone. One population expressed a gene signature associated with the initiation of PC differentiation and had an enhanced propensity to form PCs in vitro. Unexpectedly, the estimated affinity of this putative pre-PC population was indistinguishable from cells in the GC generally. This was also true when high- or low-avidity recombinant PfCSP proteins were used as immunogens. Immunization with low-avidity PfCSP did, however, induce increased affinity maturation. Collectively these findings suggest that the initiation of PC development in the GC occurs via an affinity independent process.

2024-01-15 | GSE248255 | GEO

Lack of affinity signature for germinal center cells that have initiated plasma cell differentiation (Figure2)

2024-01-15 | GSE227370 | 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

Lack of affinity signature for germinal center cells that have initiated plasma cell differentiation

Project description:This SuperSeries is composed of the SubSeries listed below.

2024-01-15 | GSE248377 | GEO

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

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

| PRJNA1032633 | ENA

Continuous Germinal Center Invasion Contributes to the Diversity of the Immune Response

Project description:Antibody responses are characterized by increasing affinity and diversity over time. Affinity maturation occurs in germinal centers by a mechanism that involves repeated cycles of somatic mutation and selection. How antibody responses diversify while also undergoing affinity maturation is not as well understood. Here, we examined germinal center (GC) dynamics by tracking B cell entry, division, somatic mutation and specificity. Our experiments show that naïve B cells continuously enter GCs where they compete for T cell help and undergo clonal expansion. Consistent with late entry, invaders carry fewer mutations but can contribute up to 30 % or more of the cells in late-stage germinal centers. Notably, cells entering the germinal center at later stages of the reaction diversify the immune response by expressing receptors that show low affinity to the immunogen. Paradoxically, the affinity threshold for late GC entry is lowered in the presence of high affinity antibodies.

2023-01-11 | GSE218272 | GEO

Csk restrains BCR-mediated ROS production and contributes to germinal center selection and affinity maturation

Project description:Compared with naïve B cells, the B cell receptor (BCR) signal in germinal center (GC) B cells is attenuated; however, the significance of this signaling attenuation has not been well defined. Here, to investigate the role of attenuation of BCR signaling, we employed a Csk mutant mouse model in which Csk-deficiency in GC B cells resulted in augmentation of net BCR signaling with no apparent effect on antigen presentation. We found that Csk is required for GC maintenance and efficient antibody affinity maturation. Mechanistically, ROS-induced apoptosis was exacerbated concomitantly with mitochondrial dysfunction in Csk-deficient GC B cells. Hence, our data suggest that attenuation of the BCR signal restrains hyper-ROS production, thereby protecting GC B cells from apoptosis and contributing to efficient affinity maturation.

2024-05-06 | GSE244802 | 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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