Rogue B cells
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB31688 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Reemergence of pathogenic, autoantibody-producing B-cell clones in myasthenia gravis following B-cell depletion therapy
| PRJNA886711 | ENA
Project description:Myasthenia gravis (MG) is an autoantibody-mediated autoimmune disorder of the neuromuscular junction. Some patients with MG have pathogenic mAbs that recognize muscle-specific tyrosine kinase (MuSK). Patients respond well to CD20-mediated B-cell depletion therapy (BCDT); most achieve complete stable remission. However, relapse often occurs. To further understand the immunomechanisms underlying relapse we sought to study autoantibody-producing B-cells over the course of BCDT. We developed a monomeric fluorescently labelled antigen to enrich for MuSK-specific B-cells, which was validated with a novel Nalm6 cell line engineered to express a human MuSK autoantibody as B-cell receptor. We found that MuSK-specific B-cells are rare within the circulation (<3 per 10 million cells). From two MuSK-specific B-cells isolated from two distinct patients, we generated human recombinant MuSK mAbs. The autoantibodies originated from plasmablasts, used the IgG4 subclass, recognized the Ig1-like domain of MuSK and showed pathogenic capacity using an in vitro AChR clustering assay. Persistent clones of the mAbs were identified through B-cell repertoire tracing. Clonal variants of 2E6 were detected at several timepoints spanning more than five years months and reemerged after BCDT-mediated remission, appearing several months prior to relapse. These results indicate that a reservoir of rare pathogenic MuSK autoantibody-expressing B cell clones survive BCDT, then reemerge prior to manifestation of clinical relapse. This study provides both a mechanistic understanding of MuSK MG relapse and a valuable candidate biomarker for relapse prediction.
2022-11-07 | GSE215237 | GEO
Project description:Genetic techniques such as antibody phage display have indicated an oligoclonal autoantibody response in various autoimmune diseases including pemphigus. These techniques have limited sampling of B cell clones. Characterization by mass spectometry of pemphigus serum autoantibodies affinity-purified on the autoantigen desmoglein indicates a much more polyclonal response. Conversely, many genetically detectable anti-desmoglein B cells do not contribute detectably to the serum antibody response. There is no convergence of the autoantibody response among patients, as determined by CDR3 sequence or heavy chain variable gene usage, implying targeting of these genes will not be a useful therapeutic strategy. Longitudinal analysis of autoantibodies over years indicates that, although many antibody clones persist, the proportion of each clonal antibody changes. These studies indicate a dynamic and very diverse autoantibody response not revealed by genetic studies, and explain why similar overall anti-desmoglein titers may give variable disease activity.
2016-11-30 | MSV000080368 | MassIVE
Project description:We performed single-cell transcriptome analysis (using MARS-seq and 10x) of four human cell lines, as well as bulk tracscriptome analysis of hundreds of single-cell clones, derived from the same cells population. Additionally, we performed methylation analysis of HCT116 single cells (using whole-genome PBAT) and of the same clones whose transcriptome was analysed (using capture-PBAT). We also analyse longitudinal single cell transcriptomes of six selected HCT116 clones grown for up to 148 days in our lab, and analysed cells and clones of HCT116 cells harbouring knock-out mutations in DNMT1 and DNMT3B (DKO).
2020-01-29 | GSE144357 | GEO
Project description:To better understand the role of follicular T cells in autoantibody-mediated disease, we performed single cell RNA and T cell receptor (TCR) sequencing of follicular T cells in a mouse model of autoantibody-mediated disease. This repository provides paired transcriptomes and unbiased TCRab repertoires from sorted CD4+CXCR5+PD1+ follicular T cells at single cell resolution. Our analysis revealed that a minority of clonotypes are preferentially shared amongst autoimmune follicular T cells, and clonotypic expansion is associated with differential gene signatures in autoimmune disease. These data provide insight into the phenotypic differences of follicular T cells in B cell-driven autoimmune disease versus foreign immunization.
2021-09-20 | GSE157649 | GEO
Project description:In this experiment we generated Affymetrix gene expression data for T Follicular Helper (TFH) cells from tonsils of healthy volunteers (4 biological replicates) and naive CD4-positive helper T cells (2 biological replicates). TFH cells provide a model relevant to SLE as TFH operate upstream of the activation of pathogenic autoantibody-producing B cells during the disease. This experiment accompanies promoter capture-C and ATAC-seq experiments on the same cell types.
2019-04-01 | E-MTAB-6637 | biostudies-arrayexpress
Project description:The presence of autoantibodies is a defining feature of many autoimmune diseases. The number of unique autoantibody clones is conceivably limited by immune tolerance mechanisms, but unknown due to limitations of the currently applied technologies. Here, we introduce an autoantigen-specific liquid chromatography-mass spectrometry-based IgG1 Fab profiling approach using the anti-citrullinated protein antibody (ACPA) repertoire in rheumatoid arthritis (RA) as an example. We show that each patient harbors a unique and diverse ACPA IgG1 repertoire dominated by only a few antibody clones. In contrast to the total plasma IgG1 antibody repertoire, the ACPA IgG1 sub-repertoire is characterized by an expansion of antibodies that harbor one, two or even more Fab glycans, and different glycovariants of the same clone can be detected. Together, our data indicate that the autoantibody response in a prominent human autoimmune disease is complex, unique to each patient and dominated by a relatively low number of clones.
2023-10-26 | MSV000093196 | MassIVE
Project description:Transcriptome analysis of single cell-derived hiPSC-lt-NES cell clones
| PRJNA699050 | ENA
Project description:We found a high frequency of heterozygous Fanconi-BRCA pathway mutations in pediatric T-ALL. BRCA2 was the most commonly mutated gene. We transduced Cas9-expressing Jurkat cells, which lacked an identifiable BRCA2 mutation, with an integration-defective lentiviral guide RNA expression construct targeting exon 11 of BRCA2 (NM_000059). Single-cell cloning and sequencing analysis revealed two distinct clones harboring monoallelic BRCA2 frameshift mutations, termed clones W4 and W5. Each of these clones was subjected to RNA sequencing analysis.
2019-02-20 | GSE126780 | GEO
Project description:Biomarkers are needed to accurately predict and monitor type 1 diabetes progression during the substantially heterogeneous presymptomatic period of the disease development. To address this concern, we studied temporal changes in the plasma and serum proteomes of < 5-year-old children with HLA-conferred risk for type 1 diabetes by analysing longitudinal sample series that were collected at regular intervals between birth and diagnosis. Using mass spectrometry-based discovery proteomics, longitudinal plasma sample series from multiple autoantibody positive children who had rapidly progressed to type 1 diabetes before 4 years of age were analysed and compared with similar measurements from age and gender matched children who were either single autoantibody positive or autoantibody negative. Following analysis of the data with an additive Gaussian process regression model (LonGP), targeted proteomics was used to verify 11 biomarker candidates in a larger independent yet similar cohort of children with more frequent sampling points. The data reiterated extensive age related trends for protein levels in young children. Further, by combining the utility of LonGP together with the targeted analysis in an extended cohort, these analyses demonstrated that the serum levels of two peptides unique for apolipoprotein C1 (APOC1) were decreased after the appearance of the first autoantibody and remained relatively less abundant in children who progressed to type 1 diabetes in comparison to autoantibody negative children.
2023-09-26 | PXD033744 | Pride