Elevated circulating CD19+CD24hiCD38hi B cells display pro-inflammatory phenotype in idiopathic membranous nephropathy

Abstract

CD19⁺CD24^hiCD38^hi regulatory B cells exert immunosuppressive functions by producing IL-10, but their role in idiopathic membranous nephropathy (IMN) remains elusive. Here, we investigated the frequency and functional changes of circulating CD19⁺CD24^hiCD38^hi B cells and evaluated the correlation of CD19⁺CD24^hiCD38^hi B cells with clinical features and T helper cell subsets in IMN patients. Compared with healthy controls (HCs), IMN patients showed an increased frequency of CD19⁺CD24^hiCD38^hi B cells, but a significant reduction in the percentage of CD19⁺CD24^hiCD38^hi B cells was observed 4 weeks after cyclophosphamide treatment. The frequency of CD19⁺CD24^hiCD38^hi B cells was positively correlated with the levels of 24h urinary protein, but negatively correlated with serum total protein and serum albumin, respectively. CD19⁺CD24^hiCD38^hi B cells in IMN patients displayed a skewed pro-inflammatory cytokine profile with a higher level of IL-6 and IL-12, but a lower concentration of IL-10 than their healthy counterparts. Accompanied by upregulation of Th2 and Th17 cells in IMN patients, the percentage of CD19⁺CD24^hiCD38^hi B cell subset was positively associated with Th17 cell frequency. In conclusion, CD19⁺CD24^hiCD38^hi B cells were expanded but functionally impaired in IMN patients. Their altered pro-inflammatory cytokine profile may contribute to the pathogenesis of IMN.

Keywords: Autoimmune disease; CD19(+)CD24(hi)CD38(hi) B cells; Idiopathic membranous nephropathy; Regulatory B cells; T helper 17 cells.