Antigen-experienced CXCR5- CD19low B cells are plasmablast precursors expanded in SLE

Szelinski, F.; Stefanski, A.-L.; Wiedemann, A.; Schrezenmeier, E.; Rincon-Arevalo, H.; Reiter, K.; Lettau, M.; Dang, V. D.; Fuchs, S.; Frei, A. P.; Alexander, T.; Lino, A. C.; Dörner, T.

B 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-CD19high and CXCR5-CD19low. Here, we characterize a hitherto unknown antigen-experienced CXCR5-CD19low B cell subsets enhanced in SLE and carrying a plasmablast (PB) phenotype enriched for switched immunoglobulins, and expressing CD38, CD95, CD71, PRDM1, XBP-1, and IRF4. CXCR5-CD19low resemble activated B cells with a characteristically diminished B cell receptor responsiveness. CXCR5-CD19low B cells increased with PB frequencies in SLE and upon BNT162b2 vaccination suggesting their interrelationship. Our data suggest that CXCR5-CD19low B cells are precursors of plasmablasts, thus co-targeting this subset may have therapeutic value in SLE.