CD5+ B cells from individuals with systemic lupus erythematosus express granzyme B

Recently, we reported that IL‐21 induces granzyme B (GzmB) and GzmB‐dependent apoptosis in malignant CD5⁺ B cells from patients with chronic lymphocytic leukemia. Several autoimmune diseases (AD) are associated with enhanced frequencies of CD5⁺ B cells. Since AD are also associated with elevated IL‐21 and GzmB levels, we postulated a link between CD5⁺ B cells, IL‐21 and GzmB. Here, we demonstrate that IL‐21 and GzmB serum levels are highly correlated in subjects with systemic lupus erythematosus (SLE) and that freshly isolated CD5⁺ SLE B cells constitutively express GzmB. IL‐21 directly induced GzmB expression and secretion by CD5⁺ B cells from several AD and from cord blood in vitro, and the simultaneous presence of BCR stimulation strongly enhanced this process. Furthermore, IL‐21 suppressed both viability and expansion of CD5⁺ B cells from SLE individuals. In summary, our study may explain the elevated levels of IL‐21 and GzmB in SLE and other AD. Moreover, our data suggest that IL‐21 may have disease‐modifying characteristics by inducing GzmB in CD5⁺ B cells and by suppressing their expansion. Our results provide the rationale for further evaluation of the therapeutic potential of IL‐21 in certain AD such as SLE.