B Cell Receptor Repertoire Analysis of the CD21 B Cell Compartment in Healthy Individuals, Patients With Sjögren's Disease, and Patients With Radiographic Axial Spondyloarthritis.
Rick Wilbrink, Linda van der Weele, Anneke J P L Spoorenberg, Niek de Vries, Ilse T G Niewold, Gwenny M Verstappen, Frans G M Kroese
Author Information
Rick Wilbrink: Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Linda van der Weele: Department of Rheumatology & Clinical Immunology, Amsterdam Rheumatology and Immunology Center (ARC), Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
Anneke J P L Spoorenberg: Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Niek de Vries: Department of Rheumatology & Clinical Immunology, Amsterdam Rheumatology and Immunology Center (ARC), Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
Ilse T G Niewold: Department of Rheumatology & Clinical Immunology, Amsterdam Rheumatology and Immunology Center (ARC), Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands.
Gwenny M Verstappen: Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Frans G M Kroese: Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
B cells with low or absent expression of CD21 (CD21 B cells) gained attention due to their expansion in the peripheral blood of patients with immune-mediated, rheumatic diseases. This is not only observed in typical autoimmune diseases like systemic lupus erythematosus and Sjögren's disease (SjD) but also in radiographic axial spondyloarthritis (r-axSpA), which is considered an autoinflammatory disease. To gain more insight into the origins of the heterogeneous CD21 B-cell population, and its relation to the plasmablast (PB) compartment, we profiled the B-cell-receptor (BCR) repertoire in CD27 and CD27 fractions of CD21 B cells and early PBs using next-generation sequencing. Populations were sorted from peripheral blood of healthy individuals, SjD patients, and r-axSpA patients (n = 10 for each group). In healthy individuals and both patient groups, our findings indicate that CD27CD21 B cells, which exhibit few mutations in their BCR, may develop into CD27CD21 B cells and PBs, both marked by considerably more mutations. Given the known expansion of circulating CD27CD21 B cells in SjD and r-axSpA patients and clonal relationships with both CD27CD21 B cells and early PBs, these cells might actively contribute to (pathological) immune responses in rheumatic diseases with autoimmune and/or autoinflammatory characteristics.
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