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Transcriptional profiling and clonality analysis of small intestinal and bone marrow plasma cells

This study contains single-cell RNA sequencing data (gene expression, VDJ and feature barcodes) for paired samples of small intestinal plasma cells and bone marrow plasma cells isolated from four patients with celiac disease. The mucosa lining the gastrointestinal tract harbors the body’s largest population of plasma cells, most of which produce dimeric IgA destined for release into the lumen. In addition, there is systemic production of monomeric IgA circulating in the blood. Little is known about the connection between systemic and mucosal IgA. To address this relationship and to explore antibody responses against the microbiota, we isolated bacteria from duodenal biopsies and assessed antibody reactivity. Systemic IgA showed reactivity to bacteria of the upper gastrointestinal tract with a preference for binding Neisseria species, while duodenal IgA showed broader reactivity. Single-cell RNA sequencing of gut and bone marrow plasma cells demonstrated limited clonal overlap between the two compartments. Yet, a few shared clones specific to bacterial antigens were identified. Overall, gut and bone marrow plasma cells have distinct V(D)J repertoires and IgA subclass distributions, and they likely depend on B-cell activation at discrete anatomical sites.

Type: Transcriptome Sequencing
Archiver: Federated EGA Norway

3 Datasets

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID	Description	Technology	Samples
EGAD50000002778	The dataset contains processed sequencing data from Chromium Single Cell 5’ gene expression, human B cell VDJ and feature barcode (CSP) sequencing from transglutaminase 2-specific and other small intestinal and bone marrow plasma cells isolated from four celiac disease patients. The raw sequencing data has been processed with Cell Ranger v.6.0.2 with the multi and aggr functions using the pre-built Cell Ranger references GRCh38 version 2020-A for gene expression and GRCh38-alts-ensembl-5.0.0 for V(D)J analysis. The dataset consists of a gene expression and antibody capture expression matrix (cell barcodes and feature names in tsv.gz file, expression matrix in mtx.gz file) and VDJ sequences in AIRR format (csv file). A metadata file (csv file) details cells passing our custom quality control based on number of detected genes, UMIs, mitochondrial genes, immunoglobulin genes and a productively rearranged immunoglobulin heavy chain.	Illumina NovaSeq 6000	4
EGAD50000002779	The dataset contains raw fastq files (fastq.gz) for Chromium Single Cell human B cell VDJ and feature barcode (CSP) sequencing from plasma cells isolated from paired small intestine and bone marrow samples from four celiac disease patients. The fastq files have been demultiplexed by CellRanger according to patient and library type (VDJ and CSP), with two runs (consisting of R1, R2 and index read) per subject per library type. Single cell 5’ gene expression, V(D)J-enriched and cell surface protein libraries were generated using Chromium single cell kits, and barcoded cDNA from a total of 10,000-12,000 cells was generated using the 10x Genomics Chromium Controller. The libraries were pooled prior to sequencing on a NovaSeq 6000 instrument (Illumina) with 150 bp paired-end reads.	Illumina NovaSeq 6000	4
EGAD50000002780	The dataset contains raw fastq files (fastq.gz) for Chromium Single Cell 5’ gene expression (GEX) and feature barcode (CSP) sequencing from plasma cells isolated from paired small intestine and bone marrow samples from four celiac disease patients. The fastq files have been demultiplexed by CellRanger according to patient and library type (GEX and CSP), with two runs (consisting of R1, R2 and index read) per subject per library type. Single cell 5’ gene expression, V(D)J-enriched and cell surface protein libraries were generated using Chromium single cell kits, and barcoded cDNA from a total of 10,000-12,000 cells was generated using the 10x Genomics Chromium Controller. The libraries were pooled prior to sequencing on a NovaSeq 6000 instrument (Illumina) with 150 bp paired-end reads.	Illumina NovaSeq 6000	4