Antigen-experienced CXCR5^-CD19^lowB cells are plasmablast precursors expanded in SLE

AbstractB cells play a critical role in the pathogenesis of systemic lupus erythematosus (SLE). We analysed two independent cohorts of healthy donors and SLE patients using a combined approach of flow and mass cytometry. We have found that IgD-CD27+switched and atypical IgD-CD27-memory B cells, which are increased in SLE, represent heterogeneous populations composed each of three different subsets, such as CXCR5+CD19int, CXCR5-CD19highand CXCR5-CD19low. Here, we characterize a hitherto unknown antigen-experienced CXCR5-CD19lowB cell subsets enhanced in SLE and carrying a plasmablast (PB) phenotype enriched for switched immunoglobulins, and expressing CD38, CD95, CD71,PRDM1, XBP-1, andIRF4. CXCR5-CD19lowresemble activated B cells with a characteristically diminished B cell receptor responsiveness. CXCR5-CD19lowB cells increased with PB frequencies in SLE and upon BNT162b2 vaccination suggesting their interrelationship. Our data suggest that CXCR5-CD19lowB cells are precursors of plasmablasts, thus co-targeting this subset may have therapeutic value in SLE.