Rogue B cells
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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:Previous lineage analyses have shown that retinal progenitor cells (RPCs) are multipotent throughout development, and expression profiling studies have shown a great deal of molecular heterogeneity among RPCs. To determine if the molecular heterogeneity predicts that an RPC will produce particular types of progeny, clonal lineage analysis was used to investigate the progeny of a subset of RPCs, those that express the basic helix-loop-helix (bHLH) transcription factor, Olig2. In contrast to the large and complex set of clones generated by viral marking of random embryonic RPCs, the embryonic Olig2+ RPCs underwent terminal divisions, producing small clones with primarily two of the five cell types being made by the pool of RPCs at that time. The embryonically produced cell types made by Olig2+ RPCs were cone photoreceptors and horizontal cell (HC) interneurons. Moreover, the embryonic Olig2+ RPC did not make the later Olig2+ RPC. The later, postnatal Olig2+ RPCs also made terminal divisions, which were biased towards production of rod photoreceptors and amacrine cell (AC) interneurons. These data indicate that the multipotent progenitor pool is made up of distinctive types of RPCs, which have biases towards producing subsets of retinal neurons in a terminal division, with the types of neurons produced varying over time. This strategy is similar to that of the developing Drosophila melanogaster ventral nerve cord, with the Olig2+ cells behaving as ganglion mother cells. Single retinal cells were isolated in tubes containing lysis buffer, their mRNAs were reverse transcribed, and the resulting cDNAs were PCR amplified for 35 cycles. Labeled cDNA samples were hybridized to Affymetrix 430 2.0 microarrays and the data was normalized using MAS5.0 software. These cells were examined for the expression of Olig2 or other bHLH factors.
2012-04-12 | E-GEOD-37207 | biostudies-arrayexpress