TRANSPLANTATION CD24 hi CD27 1 and plasmablast-like regulatory B cells in human chronic graft-versus-host disease

pathogenesis of chronic graft-versus-host disease (cGVHD) after allogeneic stem cell transplantation. Here, we found a relation between decreased Breg frequencies and cGVHD severity. An impaired ability of B cells to produce IL-10, possibly linked to poor signal transducer and activator of transcription 3 and extracellular signal-regulated kinase phosphorylation, was found in patients with active cGVHD. IL-10 production was not confined toasingleB-cellsubset,but enriched inboththeCD24 hi CD27 1 andCD27 hi CD38 hi plasmablast B-cell compartments. In vitro plasmablast differentiation increased the frequency of IL-10–producing B cells. We confirmed that allogeneic transplant recipients had an impaired reconstitution of the memory B-cellpool.cGVHDpatientshadlessCD24 hi CD27 1 BcellsandIL-10–producingCD24 hi CD27 1 Bcells.PatientswithcGVHDhadincreased plasmablast frequencies but decreased IL-10–producing plasmablasts. These results suggest a role of CD24 hi CD27 1 B-cell and plasmablast-derived IL-10 in the regulation of human cGVHD. ( Blood . 2015;125(11):1830-1839) Here, we prospectively studied Bregs and B-cell subsets in 69 AHSCT recipients. Our results suggest that Bregs are enriched in both the CD24 hi CD27 1 B-cell subset and CD24 2 CD27 hi CD38 hi plasmablast cell compartments. In vitro differentiation of human B cells into plasmablasts and plasma cells increased IL-10 – producing B-cell numbers. Allogeneic transplant recipients with cGVHD had decreased Bregs and IL-10 – producing plasmablast counts as compared with AHSCT recipients with no cGVHD. This suggests a novel role of CD24 hi CD27 1 B-cell – and plasmablast-derived IL-10 in the regulation of human cGVHD.