Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Transcriptional profiling of mouse germinal center B cells (B220+, GL7+, CD95+) isolated from GC-specific (Cg1-Cre) DAF-TM transgenic or control mice

ABSTRACT: Germinal centers (GCs) support diversification and affinity maturation of antibody repertoires through iterative cycles of T-cell-dependent positive selection, B cell clonal expansion and antigen-receptor hypermutation. Positive selection is critical for efficient affinity maturation and depends on only partially understood signaling processes. We show that BCL6-dependent physiological repression of decay accelerating factor (DAF/CD55) on GC B cells is critical for effective positive selection and affinity maturation during GC responses. Absence of DAF on GC B cells lifts restraint on local complement activation, yielding autocrine C3a/C5a-receptor signaling that is indispensable for CD40-dependent mTOR pathway activation during positive selection. Genetic disruption of this pathway causes premature GC collapse and impairs affinity maturation. These results identify previously undiscerned targets to therapeutically manipulate protective and potentially injurious humoral immune responses.

ORGANISM(S): Mus musculus

PROVIDER: GSE148570 | GEO | 2021/03/22

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

The RNA binding protein PTBP1 is necessary for B cell selection in germinal centres

Project description:Antibody affinity maturation occurs in germinal centres (GC) where B cells cycle between the light zone (LZ) and the dark zone. In the LZ GC B cells bearing immunoglobulins with the highest affinity for antigen receive positive selection signals from T helper cells that promotes their rapid proliferation. Here we show that the RNA binding protein PTBP1 is necessary for the progression of GC B cells through late S-phase of the cell cycle and for affinity maturation. PTBP1 is required for the expression of the c-MYC-dependent gene programme induced in GC B cells receiving T cell help and directly regulates the alternative splicing of transcripts increased during positive selection to promote anabolic metabolism and cell proliferation.

2017-12-06 | GSE100969 | GEO

RNA-seq profiles of germinal center B cells from spleens of wild-type and Il21r-deficient mice after immunization with NP-KLH

Project description:Humoral immune responses require germinal centres (GC) for antibody affinity maturation. Within GC, B-cell proliferation and mutation are segregated from affinity-based positive selection in the dark zone (DZ) and light zone (LZ) substructures, respectively. While IL21 is known to be important in affinity maturation and GC maintenance, here we show it is required for both establishing normal zone representation and preventing the accumulation of cells in G1 cell cycle stage in the GC LZ.

2021-09-22 | GSE184475 | GEO

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

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

Mapping of WT FOXO1 and M1L FOXO1 binding sites in SUDHL4 cells

Project description:The transcription factor FOXO1 directs germinal center (GC) polarity and supports affinity maturation by silencing immune activation programs in GC B cells. Recurrent somatic mutations in GC-derived B cell non-Hodgkin lymphomas (B-NHL) often target and reportedly activate FOXO1 by preventing its negative regulation by PI3K. Herein, using ad hoc mouse models, engineered cell lines and primary tumor specimens, we show instead that FOXO1 mutant proteins display altered transcriptional activities suggestive of partial loss-of-function. These defects drive simultaneous hyperactivation of signaling pathways (Stress Activated Protein Kinase -SAPK/JNK, Phosphoinositide 3-kinase -PI3K/AKT) and gene expression programs typically activated in GC B cells upon positive selection. Such changes confer mutant B cells with competitive advantages in response to key immune signals, leading to abnormal amplification of GC responses. Evidence of these FOXO1 ‘mutant’ gene programs can be found in a fraction of human B-NHL and predict clinical outcome, thus implying the frequent co-option of positive selection programs during GC-derived B-NHL pathogenesis.

2021-07-30 | GSE143774 | GEO

Transcriptional profiling of SUDHL4 cells edited by CRISPR-cas9 to induce point mutations in the FOXO1 locus

2021-07-30 | GSE143773 | GEO

Transcriptional profiling of SUDHL4 cells stimulated with megaCD40L and IgM/G for 24 hours

2021-07-30 | GSE143772 | GEO

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.

2021-04-16 | GSE154634 | 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

Transcriptional profiling of mouse germinal center B cells (B220+, GL7+, CD95+) isolated from GC-specific (Cg1-Cre) DAF-TM transgenic or control mice

Project description:Transcriptional profiling of mouse germinal center B cells (B220+, GL7+, CD95+) isolated from GC-specific (Cg1-Cre) DAF-TM transgenic or control mice

| PRJNA625050 | ENA

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data