Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Bank1 modulates the differentiation and molecular profile of key B cell populations in autoimmunity

ABSTRACT: This study aimed at defining the role of the B-cell adaptor protein BANK1 in the appearance of age-associated B cells (ABCs) in two SLE mouse models (TLR7.tg6 and Imiquimod-induced mice), crossed with Bank1-/- mice. The absence of Bank1 led to a significant reduction in ABC levels, also affecting other B cell populations. To gain deeper insights into their differentiation pathway and the impact of Bank1 on B cell populations, a single-cell transcriptome assay was performed. In the TLR7.tg6 model, we identified 10 clusters within B cells, including an ABC-specific cluster which was decreased in Bank1-deficient mice. In its absence, ABCs exhibited an anti-inflammatory gene expression profile, while being pro-inflammatory in Bank1-sufficient lupus mice. Trajectory analyses revealed that ABCs originated from marginal zone and memory-like B cells, ultimately acquiring transcriptional characteristics associated with atypical memory cells and long-lived plasma cells. Also, Bank1 deficiency normalized the presence of naïve B cells, which were nearly absent in lupus mice. Interestingly, Bank1 deficiency significantly reduced a distinct cluster containing IFN-responsive genes. These findings underscore the critical role of Bank1 in ABC development, impacting early B cell stages towards ABC differentiation, and the presence of IFN-stimulated gene-containing B cells, both populations determinant for autoimmunity.

ORGANISM(S): Mus musculus

PROVIDER: GSE271694 | GEO | 2024/09/17

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

B cell-intrinsic IFN-g promotes CD11c+ age-associated B cell differentiation and compromises affinity-based germinal center selection in lupus

Project description:Lupus patients respond less efficiently to vaccinations and are more susceptible to infections. Previously, we have shown, in lupus models, that excessive CD11c+ age-associated B cells (ABCs) not only contribute to autoantibody production but also compromise antigen-specific germinal center (GC) B cell selection and affinity maturation by promoting aberrant T cell activation. Yet, how CD11c+ ABC differentiation is regulated is not fully understood. Here we show that B cell-intrinsic IFN-γ is required for excessive CD11c+ ABC differentiation in lupus mice. B cell-intrinsic IFN-γ is mainly produced by CD11c+ ABCs. IFN-γ-deficiency leads to decreased expression of ABC characteristic genes, including Zeb2, an ABC-specific transcription factor recently described. We further show that ablating IFN-γ can normalize T cell overactivation and rescue antigen-specific GC responses in lupus mice. Our study offers insight into the crucial role of B cell-intrinsic IFN-γ in promoting CD11c+ ABC differentiation and compromising affinity-based germinal center selection and affinity maturation in lupus, providing a potential target for lupus treatment.

2024-07-13 | GSE271698 | GEO

The transcription factor ZEB2 drives formation of age-associated B cells

Project description:Age-associated B cells (ABCs) accumulate during infection, aging and autoimmunity, contributing to lupus pathogenesis. Here, we screened for transcription factors driving ABC formation and found Zeb2 was required for human and mouse ABC differentiation in-vitro. ABCs were reduced in ZEB2 haploinsufficient individuals and in mice lacking Zeb2 in B cells. In mice with TLR7-driven lupus, Zeb2 was essential for ABC formation and autoimmune pathology. Zeb2 binds to the +20kb intronic enhancer of Mef2b, repressing Mef2b-mediated germinal center B cell differentiation and promoting ABC formation. Zeb2 also targets genes important for ABC specification and function including Itgax. Zeb2-driven ABC differentiation required Jak-Stat signaling, and treatment with the Jak1/3 inhibitor tofacitinib reduced ABC accumulation in mice and autoimmune patients. Zeb2 thus emerges as a driver of B-cell autoimmunity.

2023-12-31 | GSE242611 | GEO

IL-13Ra1-mediated signaling regulates ABC expansion and lupus pathogenesis

Project description:ABCs are an emerging B cell subset that aberrantly expand in SLE. ABC generation and differentiation exhibit marked sexual dimorphism and TLR7 engagement is a key contributor to these sex differences. ABC generation is also controlled by IL-21 and its interplay with IFNg and IL-4. Here we investigated whether IL-13Ra1, an X-linked receptor that transmits IL-4/IL-13 signals, can regulate ABCs and lupus pathogenesis.

2022-06-16 | GSE206012 | GEO

Age-Associated B Cells are Heterogenous and Dynamic in Autoimmunity

Project description:Age-Associated B Cells (ABCs) are a population of CD11c+ and/or CD11b+ B cells expanded in autoimmune lupus. To understand potential heterogeneity within ABCs and the relationship of ABCs to other splenic B cell subsets, we performed scRNA-seq with 5' V(D)J and CITE-seq cell surface features using the 10x Genomics Chromium platform on total splenic CD19+ B cells sorted from lupus-prone MRL/lpr. We found that ABC are a distinct transcriptional lineage that resolved into two related clusters. Analysis of BCR heavy chains identified clones present in both ABC and plasmablast compartments. Inferred lineage trees based on V gene somatic hypermutation suggested that self-renewing ABC feed into the plasmablast compartment repeatedly while continuing to themselves undergo mutation and expansion.

2023-01-01 | GSE202110 | GEO

Sex-specific differences in the function and differentiation of ABCs contribute to the female bias in lupus pathogenesis

Project description:We report the application of RNA-seq, ATAC-seq, and CUT and RUN technology for high-throughput profiling of H3K27me3 epigenetic marks in mice SWAP-70 and DEF6 double knockout (DKO) B-lymphocytes (ABCs and FoBs) flow sorted from spleen. We show that ABCs from female and male DKO mice have unique transcriptional profiles, chromatin accessibility, and that there is a selective loss of repressive chromatin marks like H3K27me3 in ABCs of DKO females can contribute to the increased expression of X-chromosome linked genes like Tlr7 and several other loci among which Tbx21, the classical ABC marker, showed strongest loss in F-ABCs as compared to F-FoBs.

2021-05-24 | GSE175365 | GEO

Zeb2 drives the formation of CD11c+ atypical B cells to sustain germinal centers that control persistent infection [Bulk RNA-seq]

Project description:CD11c+ atypical B cells (ABCs) are an alternative memory B cell lineage associated with immunization, infection, and autoimmunity. However, the factors that drive the transcriptional program of ABCs have not been identified, and the function of this population remains incompletely understood. Here we identified candidate transcription factors associated with the ABC population based on a human tonsillar B cell single cell dataset. We identified CD11c+ B cells in mice with a similar transcriptomic signature to human ABCs, and using an optimized CRISPR-Cas9 knockdown screen, we observed that loss of zinc finger E-box binding homeobox 2 (Zeb2) impaired ABC formation. Furthermore, ZEB2 haplo-insufficient Mowat Wilson syndrome (MWS) patients have decreased circulating ABCs in the blood. In Cd23Cre/+Zeb2fl/fl mice with impaired ABC formation, ABCs were dispensable for efficient humoral responses after Plasmodium sporozoite immunization but were required to control recrudescent blood-stage malaria. Immune phenotyping revealed that ABCs drive optimal T follicular helper (Tfh) cell formation and germinal center (GC) responses and they reside at the red/white pulp border likely permitting better access to pathogen antigens for presentation. Collectively, our study shows that ABC formation is dependent upon Zeb2, and these cells can limit recrudescent infection by sustaining GC reactions.

2024-02-09 | GSE213194 | GEO

Zeb2 drives the formation of CD11c+ atypical B cells to sustain germinal centers that control persistent infection [CITE-seq and scRNA-seq]

2024-02-09 | GSE213186 | GEO

Role of SWEF proteins in ABC differentiation

Project description:Age/autoimmune-associated B cells (ABCs) are a T-bet dependent B cell subset, which accumulates prematurely in autoimmune settings. The molecular pathways that regulate ABCs in autoimmunity are largely unknown. The SWEF proteins include SWAP-70 and DEF6, a newly identified SLE risk variant. SWEF-deficient mice (double knock-out=DKO) develop a lupus like syndrome, which is accompanied by a marked expansion of ABCs. The accumulation of ABCs in DKO mice provided us with a unique opportunity to gain new insights into the molecular features that characterize the ABCs that prematurely expand in autoimmune conditions. Splenic Follicular B cells (FoB, B220+CD19+CD23+CD11c-CD11b-) and ABCs (B220+CD19+CD11c+CD11b+) were FACS sorted from >20 weeks old WT or DKO female mice and RNA-seq was employed to compare the transcriptome of DKO ABCs to that of FoB cells derived from either WT or DKO mice. Here we show that loss of SWEF proteins leads to altered gene expression in B cells independently of their differentiation state. In addition, a subset of genes was uniquely regulated in ABCs from DKO mice as compared to FoB cells from either WT or DKO mice. Ananlysis of the ATAC-seq experiment show that the ABCs that expand aberrantly in the DKO autoimmune setting exhibit a unique chromatin landscape and ABC-specific accessible loci displayed enrichment in AP-1/BATF, IRF, and T-bet binding motifs. Together our findings suggest that absence of SWEF proteins affects several key processes in ABCs. In particular, we observed alterations in a number of pathways involved in the control of cellular proliferation and inflammation, a finding that may play a crucial role in the premature accumulation of ABCs in DKOs and could distinguish them from non-autoimmune ABCs.

2018-03-01 | GSE99480 | GEO

RNA-seq of in vitro derived B cells

Project description:IFN-γ has been reported to be the ABC-promoting cytokine combined with signaling from IL-21, CD40L, Ag-BCR and TLR7 agonist. Hence, we adopted the in vitro differentiation cocktails (anti-IgM, R848, anti-CD40, IL-21 plus IFN-γ or IL-4) to determine the role of IFN-γ in ABC differentiation. Mouse splenic B cells were purified by negative selection and cultured in the presence of the above cocktails. Compared with IL-4, IFN-γ-polarized cells preferentially differentiated to ABC-like cells. And RNA-seq were performed on IFN-γ-polarized cells and IL-4-polarized cells.

2023-02-17 | E-MTAB-12569 | biostudies-arrayexpress

RNA-seq data of ABC from Bm12-induced lupus model

Project description:Age-associated B cells (ABCs) accumulate in systemic autoimmunity, and contributes to pathogenesis. ABCs are characterized by high expression of CD11c and T-bet. As a transcription factor, T-bet cannot be labeled in live cells with antibodies, so we constructed a reporter mouse strain in which fluorescent protein tdTomato fused to T-bet. Then we sorted ABCs (CD11c+T-bet+CD21- B cell) and non-ABCs (CD11c-T- bet- B cell) from the Bm12-induced lupus model for RNA sequencing.

2023-02-16 | E-MTAB-12568 | biostudies-arrayexpress

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