Several regulatory B lymphocyte (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). Bloods from NIU patients with active disease (n=13), in remission (n=37) and healthy controls (n=10) were immunophenotyped for CD19+CD24hiCD38lo, CD19+CD24hiCD38hi immature (iBreg) and CD19+CD38intCD24int-mature Breg. In NIU, levels of peripheral blood iBreg and serum IL-10 were decreased in active disease vs. remission (P<0.01). In quiescent NIU, iBreg 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, transitional 2 marginal-zone precursor CD19+CD21hiCD24hiCD23+-T2-MZP and marginal-zone B CD19+CD21hiCD23--MZB Breg subsets were analyzed 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 = 0.048, R2 = 0.47). Blood-derived IL-10-expressing B10 and B1 Breg cells 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 iBreg in NIU and IL-10-expressing B10 Bregs in EAU.
Chen et al. (Wed,) studied this question.