IL-27 directly enhances germinal center b cell activity and potentiates lupus in sanroque mice

Germinal centers (GC) give rise to high-affinity and long-lived Abs and are critical in immunity and autoimmunity. IL-27 supports GCs by promoting survival and function of T follicular helper cells. We demonstrate that IL-27 also directly enhances GC B cell function. Exposure of naive human B cells to rIL-27 during in vitro activation enhanced their differentiation into CD20⁺CD38⁺ CD27lowCD95⁺CD10⁺ cells, consistent with the surface marker phenotype of GC B cells. This effect was inhibited by loss-of-function mutations in STAT1 but not STAT3. To extend these findings, we studied the in vivo effects of IL-27 signals to B cells in the GC-driven Roquinsan/san lupus mouse model. Il27ra2/2Roquinsan/san mice exhibited significantly reduced GCs, IgG2a(c)⁺ autoantibodies, and nephritis. Mixed bone marrow chimeras confirmed that IL-27 acts through B cell-and CD4⁺ T cell-intrinsic mechanisms to support GCs and alter the production of pathogenic Ig isotypes. To our knowledge, our data provide the first evidence that IL-27 signals directly to B cells promote GCs and support the role of IL-27 in lupus.