Regulatory B-cells are reduced in the blood in patients with granulomatosis with polyangiitis, and fail to regulate T-cell IFN-γ production

Regulatory B (Breg) cells can dampen inflammation, autoreactivity and transplant rejection. We investigated the frequencies, phenotypes and function of Breg cells in granulomatosis with polyangiitis (GPA) to gain further knowledge to whether there are numerical alterations or limitations of their ability to regulate T-cell function. Frequencies and phenotypes of CD24 hiCD27 + and CD24 hiCD38 hi B-cells in the blood were determined with flow cytometry in 37 GPA patients (22 in remission and 15 with active disease) and 31 healthy controls (HC). A co-culture model was used to study the capacity of Breg cells to regulate T-cell activation and proliferation in cells from 10 GPA patients in remission and 12 HC. T-cell cytokine production in vitro and levels in plasma were determined with ELISA. Frequencies of CD24 hiCD27 + B-cells were reduced both during active disease and remission compared with HC (p=0.005 and p=0.010, respectively), whereas CD24 hiCD38 hi B-cells did not differ. Patient CD24 hiCD27 + B-cells exhibited decreased expression of CD25 but increased expression of PD-L1 and PD-L2 during remission. B-cells from GPA patients regulated T-cell proliferation but failed to regulate IFN-γ production [median T-cells alone 222 ng/ml vs T cells + B-cells 207 ng/ml, p=0.426). IFN-γ were also elevated in patient plasma samples (p=0.016). In conclusion, GPA patients exhibit altered numbers and phenotypes of CD24 hiCD27 + B-cells. This is accompanied by a disability to control T-cell production of Th1-type cytokines during remission, which might be of fundamental importance for the granulomatous inflammation that characterizes the chronic phase of this disease