Abstract 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 + CD19 int , CXCR5 - CD19 high and CXCR5 - CD19 low . Here, we characterize a hitherto unknown antigen-experienced CXCR5 - CD19 low 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 - CD19 low resemble activated B cells with a characteristically diminished B cell receptor responsiveness. CXCR5 - CD19 low B cells increased with PB frequencies in SLE and upon BNT162b2 vaccination suggesting their interrelationship. Our data suggest that CXCR5 - CD19 low B cells are precursors of plasmablasts, thus co-targeting this subset may have therapeutic value in SLE.