Selective decreases in regulatory B-cell (Breg) subsets in active uveitis: IL-10+CD19+CD24hiCD38hiBregs in patients...

Several regulatory B-cell (Breg) subsets have been implicated in autoimmune diseases. We investigated Breg subsets in non-infectious uveitis (NIU) and in mouse models of experimental autoimmune uveitis (EAU). Blood samples from NIU patients with active disease (n = 13), in remission (n = 37) and healthy controls (n = 10) were immunophenotyped for CD19+CD24hiCD38lo memory B cells, CD19+CD24hiCD38hi-immature Bregs (iBregs), and CD19+CD38intCD24int-mature Bregs. In NIU, levels of peripheral blood iBregs and serum interleukin-10 (IL-10) were decreased in active disease vs. remission (P < .01). In quiescent NIU, iBregs were isolated and, when added at increasing ratios to autologous CD3+ T cells, downregulated T-cell proliferation. In an EAU model, at peak disease, CD19+CD1dhiCD5+ B10, CD19+CD5+ B1, CD19+CD21hiCD24hiCD23+ transitional two marginal-zone precursor (T2-MZP) and CD19+CD21hiCD23- marginal-zone B (MZB) Breg subsets were analysed both phenotypically and functionally. In EAU spleens, all Breg subsets investigated were detectable, but the IL-10-expressing B10-Breg subset was immunosuppressive and inversely correlated with disease severity (P = .048, R2 = 0.47). Blood-derived IL-10-expressing B10 and B1 Bregs were increased in both adjuvant controls and EAU but were significantly reduced in clinically milder EAU. In dissociated retinal cells, only the B10-Breg subset was detectable and increased in EAU. Selective Breg subsets may be immunosuppressive, with iBregs in NIU and IL-10-expressing B10 Bregs in EAU.