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Comprehensive transcriptome characterization deciphers mechanisms underpinning the positive selection of B cells in germinal centers.

ABSTRACT: Comprehensive transcriptome characterization deciphers mechanisms underpinning the positive selection of B cells in germinal centers.

PROVIDER: PRJNA1168544 | ENA |

REPOSITORIES: ENA

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Comprehensive transcriptome characterization deciphers mechanisms underpinning the positive selection of B cells in germinal centers. [mouse short-read]

Project description:Comprehensive transcriptome characterization deciphers mechanisms underpinning the positive selection of B cells in germinal centers. [mouse short-read]

| PRJNA1168549 | ENA

Comprehensive transcriptome characterization deciphers mechanisms underpinning the positive selection of B cells in germinal centers. [mouse; short-read]

Project description:Alternative splicing (AS) and translational regulation play major roles in the activation and differentiation of immune cells. Previous studies using short-read sequencing linked individual AS events in germinal center (GC) B cells to proliferation and survival. To establish a more comprehensive understanding of transcript isoform changes that accompany B cell selection in the GC we developed a workflow for long-read nanopore sequencing. MYC expression by GC B cells marks cells undergoing a programme of AS which includes the removal of poison exons (PE) in splicing factors SRSF3 and SRSF7. These are crucial for B cell expansion and regulate transcripts encoding the translation machinery which is markedly increased upon positive selection of the GC B cell.

2024-10-04 | GSE278742 | GEO

Comprehensive transcriptome characterization deciphers mechanisms underpinning the positive selection of B cells in germinal centers.

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

2024-10-04 | GSE278743 | GEO

Myc transcriptional bursts promote B cell positive selection by T cells in germinal centers

Project description:Antibody affinity maturation occurs in secondary lymphoid organs within germinal centers (GCs) where B cells mutate their antibody-encoding genes in the dark zone (DZ) followed by a selection of the high-affinity variants in the light zone (LZ) by T cells. The amount of the T cell-derived selection signals is proportional to the BCR affinity and the magnitude of Myc expression. However, since the lifetimes of Myc mRNA and protein are extremely short, it is unclear how high levels of Myc are maintained in the GC B cell to allow positive selection. Here, by measuring Myc transcripts in situ at the single-cell level, we find that T cell help promotes the frequency of Myc transcriptional bursts. T cell help primarily increases the number of Myc-positive cells rather than the amount of Myc per cell. Measurement of Myc intronic and exonic transcripts in situ demonstrates that positive selection is mediated by Myc transcriptional bursts through a rapid increase in the active transcription sites rather than an elevation in transcription rate or gene accessibility. Thus, the amount of Myc transcriptional bursts over time in the LZ, rather than Myc abundance, dictates B cell selection in germinal centers.

2024-10-15 | GSE237128 | GEO

Peyer’s Patch Germinal Centers Select Innate-like BCRs

Project description:Peyer’s Patch Germinal Centers Select Innate-like BCRs

| PRJNA591005 | 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

Myc transcriptional bursts promote B cell positive selection by T cells in germinal centers

Project description:Myc transcriptional bursts promote B cell positive selection by T cells in germinal centers

| PRJNA994027 | ENA

B cell receptor signaling in germinal centers prolongs survival and primes B cells for selection [bulk RNA-seq]

Project description:Germinal centers (GCs) are sites of B cell clonal expansion, diversification, and antibody affinity selection. This process is limited and directed by T follicular helper cells that provide helper signals to B cells that endocytose, process, and present cognate antigens in proportion to their B cell receptor (BCR) affinity. Under this model, the BCR functions as an endocytic receptor for antigen capture. How signaling through the BCR contributes to selection is not well understood. To investigate the role of BCR signaling in GC selection, we developed a tracker for antigen binding and presentation and a Bruton’s tyrosine kinase drug-resistant-mutant mouse model. We showed that BCR signaling per se is necessary for the survival and priming of light zone B cells to receive T cell help. Our findings provide insight into how high-affinity antibodies are selected within GCs and are fundamental to our understanding of adaptive immunity and vaccine development.

2023-03-09 | GSE225573 | GEO

B cell receptor signaling in germinal centers prolongs survival and primes B cells for selection [single cell RNA-Seq]

2023-03-09 | GSE225574 | GEO

Cytolytic CD8+ T cells infiltrate germinal centers to limit ongoing HIV replication in spontaneous controller lymph nodes

Project description:Follicular CD8+ T cells (fCD8) mediate surveillance in lymph node (LN) germinal centers against lymphotropic infections and cancers, but precise mechanisms by which these cells mediate immune control remain incompletely resolved. To address this, we investigated functionality, clonotypic compartmentalization, spatial localization, phenotypic characteristics, and transcriptional profiles of LN-resident virus-specific CD8+ T cells in persons who control HIV without medications. Antigen-induced proliferative and cytolytic potential consistently distinguished spontaneous controllers from noncontrollers. T cell receptor analysis revealed complete clonotypic overlap between peripheral and LN-resident HIV-specific CD8+ T cells. Transcriptional analysis of LN CD8+ T cells revealed gene signatures of inflammatory chemotaxis and antigen-induced effector function. In HIV controllers, the cytotoxic effectors perforin and granzyme B were elevated among virus-specific CXCR5+ fCD8s proximate to foci of HIV RNA within germinal centers. These results provide evidence consistent with cytolytic control of lymphotropic infection supported by inflammatory recruitment, antigen-specific proliferation, and cytotoxicity of fCD8s.

2023-04-20 | GSE196549 | GEO

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