Collectively, these data demonstrate that the effect of long-term B-cell depletion on humoral autoimmunity in RA is twofold: (1) direct elimination of autoreactive B cells, including ACPA-producing short-lived plasmablasts and (2) indirect interference in the differentiation of autoreactive B-cell towards ACPA-producing long-lived plasma cells. Here, PRTN3 is linked to rheumatoid arthritis.