{"database":"biostudies-arrayexpress","file_versions":[],"scores":null,"additional":{"submitter":["Inga-Lill Mårtensson"],"organism":["Homo sapiens"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/E-MTAB-11961"],"description":["In recent years, a circulating subset of B cells phenotypically negative for CD21 has been reported to be expanded in chronic infectious and autoimmune inflammatory diseases. While reports on the function of these cells differ by disease origin, their role in rheumatoid arthritis (RA) has remained elusive. Here, we combine clinical data with flow cytometric analyses for patients untreated for and newly diagnosed with RA. We show correlations between the frequency of CD21-Tbet+CD11c+ and destruction of both cartilage and bone in in the joints of patients at the time of diagnosis. Combining single-cell 5’ RNA sequencing with B-cell receptor (VDJ)-enriched sequencing, we are able to identify the Tbet+CD11c+ cells in the scRNA-seq data from untreated newly diagnosed RA patients. Further, we describe a characteristic gene expression pattern, with overrepresentation of upregulated genes involved in antigen processing and presenting processes. The same gene signature is near identically expressed by autoimmune-associated cells infiltrating synovial tissue of RA patients. Our findings suggest that Tbet+CD11c+ B cells may be poised for antigen presentation in the periphery, and could be capable of recirculating between the periphery and joint tissue, thereby promoting autoimmune responses. Overall, we demonstrate a potential pathogenic role of Tbet+CD11c+ B cells in RA, in which they contribute to joint destruction."],"repository":["biostudies-arrayexpress"],"sample_protocol":["Sequencing - 5' gene expression libraries were sequenced on a NextSeq (Illumina) with NextSeq 500/550 v2.5 Sequencing Reagent Kit (Illumina).","Nucleic Acid Extraction - CD20+CD3- B cells were electronically gated and CD27 versus IgD displayed. In this gate memory B cells were isolated by excluding CD27-IgD+ B cells and sorted as a single population using a Sony H800 cell sorter. Cell suspensions were loaded into a Chromium cell processing unit (10x Genomics, Pleasanton, CA, USA), generating gel bead-in emulsions (GEMs).","Sample Collection - Venous blood was collected in Lithium-Heparin tubes from the antecubital area of the arm of four patients with untreated early rheumatoid arthritis (RA). PBMCs were isolated using Ficoll (GE Healthcare) and frozen in 10% dimethylsulphoxide (DMSO, Sigma-Aldrich) to be stored at -150°C. Frozen PBMCs were thawed within 50 days of freezing and resuspended in RPMI-1640 10% FCS (Gibco, Thermofisher). Samples were stained with Fixable Viability Dye eFluor™ 506 (Invitrogen) to exclude dead cells.","Library Construction - 5' gene expression libraries were constructed according to standard 10x protocol, using the Chromium Single Cell V(D)J Reagent Kits (v1.1 chemistry, 10x Genomics) GEMs were used to construct sequencing libraries using the standard 10x protocol. Genomics Chromium Single Cell V(D)J Reagent Kits (5', chemistry 1.1)."],"figure_sub":["Organization","MINSEQE Score","Assays and Data","MAGE-TAB Files"],"omics_type":["Metabolomics","Unknown","Transcriptomics","Genomics","Proteomics"],"instrument_platform":["NextSeq 500"],"study_type":["RNA-seq of coding RNA from single cells"],"species":["Homo sapiens"],"pubmed_title":["An antigen processing and presenting gene signature in circulating and synovial Tbet+CD11c+ B cells suggests disease dependent functions"],"pubmed_authors":["Katrin Thorarinsdottir, Sarah McGrath Kristoffer Grimstad, Kristina Forslind, Daniel Glinatsi, Monica Leu Agelii, Timothy Sundell, Charlotte A. Jonsson, Alessandro Camponeschi, Anna-Karin Hultgård Ekwall, Anna Rudin, Andreas Tilevik, Inga-Lill Mårtensson, Inger Gjertsson","Inga-Lill Mårtensson"],"additional_accession":[]},"is_claimable":false,"name":"Single-Cell RNA-Seq of Memory B cells in Early Untreated Rheumatoid Arthritis Patients (Gene Expression Data)","description":"In recent years, a circulating subset of B cells phenotypically negative for CD21 has been reported to be expanded in chronic infectious and autoimmune inflammatory diseases. While reports on the function of these cells differ by disease origin, their role in rheumatoid arthritis (RA) has remained elusive. Here, we combine clinical data with flow cytometric analyses for patients untreated for and newly diagnosed with RA. We show correlations between the frequency of CD21-Tbet+CD11c+ and destruction of both cartilage and bone in in the joints of patients at the time of diagnosis. Combining single-cell 5’ RNA sequencing with B-cell receptor (VDJ)-enriched sequencing, we are able to identify the Tbet+CD11c+ cells in the scRNA-seq data from untreated newly diagnosed RA patients. Further, we describe a characteristic gene expression pattern, with overrepresentation of upregulated genes involved in antigen processing and presenting processes. The same gene signature is near identically expressed by autoimmune-associated cells infiltrating synovial tissue of RA patients. Our findings suggest that Tbet+CD11c+ B cells may be poised for antigen presentation in the periphery, and could be capable of recirculating between the periphery and joint tissue, thereby promoting autoimmune responses. Overall, we demonstrate a potential pathogenic role of Tbet+CD11c+ B cells in RA, in which they contribute to joint destruction.","dates":{"release":"2025-12-31T00:00:00Z","modification":"2025-12-31T02:02:12.195Z","creation":"2024-01-12T21:17:39.336Z"},"accession":"E-MTAB-11961","cross_references":{"ENA":["ERP139631"],"EFO":["EFO_0002944","EFO_0004170","EFO_0005684","EFO_0005518","EFO_0004184"]}}