B Cell Receptor Repertoire Analysis of the CD21^lo B Cell Compartment in Healthy Individuals, Patients With Sjögren's...

B cells with low or absent expression of CD21 (CD21^lo 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^lo 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^lo 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 CD27^-CD21^lo B cells, which exhibit few mutations in their BCR, may develop into CD27⁺CD21^lo B cells and PBs, both marked by considerably more mutations. Given the known expansion of circulating CD27^-CD21^lo B cells in SjD and r-axSpA patients and clonal relationships with both CD27⁺CD21^lo B cells and early PBs, these cells might actively contribute to (pathological) immune responses in rheumatic diseases with autoimmune and/or autoinflammatory characteristics.