Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Anitbody affinity birth through somatic hypermutation

ABSTRACT: Anitbody affinity birth through somatic hypermutation

PROVIDER: PRJNA1191854 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR31543360.fastq.gz	Fastqsanger.gz
	SRR31543361.fastq.gz	Fastqsanger.gz
	SRR31543362.fastq.gz	Fastqsanger.gz
	SRR31543363.fastq.gz	Fastqsanger.gz
	SRR31543364.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 16

Similar Datasets

Anitbody affinity birth through somatic hypermutation

Project description:B cell somatic hypermutation (SHM) and selection in germinal center (GC)s enhance antibody affinity to antigen. Conventional understanding holds that SHM enhances pre-existing antibody specificities, limiting the scope of SHM-based antibody evolution to those established in the primary repertoire through V(D)J recombination. By tracking pre-defined non-specific B cells, we observed consistent SHM in non-cognate antibody genes after immunization in settings of diverse, polyclonal B and T cells. Removing B cell competition enabled these non-specific yet somatically mutating antibodies to develop entirely new specificities to diverse antigens. Our findings introduce an updated model, where SHM drives antibody diversification without requiring initial antigen specificity. This reveals that B cell competition, rather than a necessity for specific affinity, limits the emergence of new affinities (termed here as affinity birth) by SHM and highlights the mammalian adaptive immune system’s capacity to explore antibody-antigen interactions beyond the epitopes targeted by the V(D)J-dependent primary antibody repertoire.

2024-12-04 | GSE283094 | GEO

Regulated somatic hypermutation enhances antibody affinity maturation

Project description:Regulated somatic hypermutation enhances antibody affinity maturation

| PRJNA1211152 | ENA

Regulated somatic hypermutation enhances antibody affinity maturation

Project description:Germinal centers (GCs) are microenvironments where B cells undergo affinity maturation through somatic hypermutation (SHM) and selection by T follicular helper (TFH) cells. While SHM introduces mutations at a fixed rate (~1x10⁻³ per base pair per division), most mutations are deleterious, particularly in high-affinity B cells undergoing many divisions. This study tests a theoretical model suggesting that high-affinity B cells optimize maturation by dividing more but mutating less per division. Data from mice immunized with SARS-CoV-2 or a model antigen support the model, showing that high-affinity B cells shorten their G0/G1 phases and reduce mutation rates, safeguarding their lineages and improving affinity maturation outcomes.

2025-01-27 | GSE287123 | GEO

UNG shapes the specificity of AID-induced somatic hypermutation

Project description:This SuperSeries is composed of the following subset Series: GSE39108: UNG shapes the specifity of AID-induced somatic hypermutation in non B cells GSE39114: UNG shapes the specifity of AID-induced somatic hypermutation in B cells Refer to individual Series

2012-07-04 | E-GEOD-39115 | biostudies-arrayexpress

Dynamic regulation of somatic hypermutation in germinal centers enables rapid B cell clonal expansion without loss of affinity

Project description:In the course of antibody affinity maturation, germinal center (GC) B cells mutate their immunoglobulin (Ig) heavy and light chain genes in a process known as somatic hypermutation (SHM). Panels of mutant B cells with different binding affinities for antigen are then selected in Darwinian fashion, leading to a progressive increase in affinity among the population. As with any Darwinian process, rare gain-of-fitness mutations must be identified while common loss-of-fitness mutations are avoided. Progressive acquisition of mutations therefore poses a risk during large proliferative bursts, when GC B cells go through several cell cycles in the absence of affinity-based selection. Using a combination of in vivo mouse experiments and mathematical modeling, we show that GCs achieve this balance by strongly suppressing SHM during clonal burst-type expansion, so that a large fraction of the progeny generated during such bursts do not deviate from their ancestral genotype. Intravital imaging and image-based cell sorting of a new CyclinE(A)/cyclin-dependent kinase 2 (CDK2) reporter mouse strain showed that B cells actively undergoing proliferative bursts lack the transient CDK2low “G0-like” phase of the cell cycle in which SHM takes place. We propose a model in which inertially cycling B cells largely delay SHM until the G0-like phase that follows their final round of division in the DZ, thus maintaining affinity as they clonally expand in the absence of selection.

2025-03-17 | GSE285185 | GEO

Topologically Associated Domains Delineate Susceptibility to Somatic Hypermutation

Project description:Topologically Associated Domains Delineate Susceptibility to Somatic Hypermutation

| PRJNA587064 | ENA

Dynamic regulation of somatic hypermutation in germinal centers enables rapid B cell clonal expansion without loss of affinity

Project description:Dynamic regulation of somatic hypermutation in germinal centers enables rapid B cell clonal expansion without loss of affinity

| PRJNA1201770 | ENA

Topologically Associated Domains Delineate Susceptibility to Somatic Hypermutation

Project description:Somatic hypermutation (SHM) introduces point mutations into immunoglobulin (Ig) genes of activated B cells to support the process of antibody affinity maturation but also causes "off-target" mutations in other parts of the genome. We have used sensitive lentiviral SHM reporter vectors and a mutationally active human B cell line to identify dozens of regions of the genome that are intrinsically susceptible to SHM ("hot" regions) and many hundreds of regions that are resistant to SHM ("cold" regions). Hot and cold regions are frequently contained within topologically associated domains (TADs). Comparison of hot and cold TADs reveals that while overall levels of transcription are equal, hot TADs are enriched for NIPBL (a component of the cohesin loader), super enhancers, markers of paused/stalled RNA polymerase 2, and multiple transcription factors implicated in B cell development and targeting of SHM. We demonstrate that at least some hot TADs contain enhancer elements that possess SHM targeting activity and that insertion of a strong Ig SHM-targeting element into a cold TAD renders it hot. Our findings lead to a model for SHM susceptibility involving the cooperative action of cis-acting SHM targeting elements and the dynamic and architectural properties of TADs.

2019-12-04 | GSE139810 | GEO

Bach2 regulates AID-mediated immunoglobulin gene conversion and somatic hypermutation in DT40 B cells

Project description:The transcription factor Bach2 is required for germinal center formation and somatic hypermutation (SHM) of immunoglobulins, both central to an efficient antibody-mediated immune response. Activation-induced cytidine deaminase (AID) initiates SHM and CSR in germinal centers and has potential to induce human B cell lymphoma. To understand the role of Bach2 in AID-mediated immunoglobulin gene diversification processes, we established a Bach2-deficient DT40 B cell line. We show that in addition to allowing SHM, Bach2 drives immunoglobulin gene conversion (GCV), an important AID-dependent antibody gene diversification process. We demonstrate that Bach2 promotes GCV by increasing the expression of AID. Importantly, we found that the regulation of AID is independent of Blimp-1 and that Bach2-deficient cells have altered expression of several genes regulating AID expression, stability and function. These results demonstrate that Bach2 has a previously unappreciated role in the production of high-affinity antibodies.

2017-03-27 | GSE92430 | 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

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