Longevity, clonal relationship, and transcriptional program of celiac disease–specific plasma cells
| Autor: | Knut E.A. Lundin, Chunyan Zhou, Jørgen Jahnsen, Shuo-Wang Qiao, Ludvig M. Sollid, Linn M Eggesbø, Ida Lindeman, Rasmus Iversen, Justyna Polak, Zhichao Miao |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Immunoglobulin gene
Glutens Transcription Genetic Tissue transglutaminase Immunology Population Antigens CD19 Longevity Plasma Cells Autoimmunity CD19 Article Cell Line Pathogenesis Transcriptome 03 medical and health sciences 0302 clinical medicine Antigen GTP-Binding Proteins Sf9 Cells Immunology and Allergy Animals Humans Protein Glutamine gamma Glutamyltransferase 2 Amino Acid Sequence education 030304 developmental biology 0303 health sciences education.field_of_study Polymorphism Genetic Transglutaminases biology Gene Expression Profiling fungi Mucosal Immunology Molecular biology 3. Good health Immunoglobulin A Celiac Disease Antibody Formation biology.protein Leukocyte Common Antigens Antibody Immunoglobulin Heavy Chains 030215 immunology |
| Zdroj: | The Journal of Experimental Medicine |
| ISSN: | 1540-9538 0022-1007 |
| Popis: | Single-cell analysis reveals an accumulation of short-lived disease-specific as well as non–disease-specific intestinal plasma cells in untreated and short-term–treated celiac disease. Plasma cells differ transcriptionally depending on specificity, longevity, and disease status and may contribute to formation of the celiac lesion. Disease-specific plasma cells (PCs) reactive with transglutaminase 2 (TG2) or deamidated gluten peptides (DGPs) are abundant in celiac disease (CeD) gut lesions. Their contribution toward CeD pathogenesis is unclear. We assessed expression of markers associated with PC longevity in 15 untreated and 26 treated CeD patients in addition to 13 non-CeD controls and performed RNA sequencing with clonal inference and transcriptomic analysis of 3,251 single PCs. We observed antigen-dependent V-gene selection and stereotypic antibodies. Generation of recombinant DGP-specific antibodies revealed a key role of a heavy chain residue that displays polymorphism, suggesting that immunoglobulin gene polymorphisms may influence CeD-specific antibody responses. We identified transcriptional differences between CeD-specific and non–disease-specific PCs and between short-lived and long-lived PCs. The short-lived CD19+CD45+ phenotype dominated in untreated and short-term–treated CeD, in particular among disease-specific PCs but also in the general PC population. Thus, the disease lesion of untreated CeD is characterized by massive accumulation of short-lived PCs that are not only directed against disease-specific antigens. Graphical Abstract |
| Databáze: | OpenAIRE |
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