Defective CD19+CD24hiCD38hitransitional B-cell function in patients with relapsing-remitting MS

Background: Multiple sclerosis (MS) is characterized by central nervous system (CNS) infiltration of T and B cells, excess inflammatory cytokine and chemokine production and failure of immune regulation. CD19+CD24(hi)CD38(hi)transitional B cells producing interleukin (IL)-10 have been shown to suppress interferon-gamma (IFN gamma) and tumour necrosis factor-alpha (TNF alpha) production by CD4+ T cells and to be dysfunctional in autoimmune arthritis and systemic lupus erythematosus. Objective: We hypothesized that transitional B-cell-dependent immune regulation could be defective in MS and examined their function in healthy subjects and patients with relapsing-remitting multiple sclerosis (RRMS). Methods: A total of 62 healthy donors and 21 RRMS subjects donated peripheral blood for the study. IL-10-producing B cells, IFN gamma and TNF alpha-producing T cells and proliferating T cells were quantified by flow cytometry. Results: In healthy individuals, CD19+CD24(hi)CD38(hi)transitional B cells produce more IL-10 than CD19+CD24+CD38+ naive and CD19+CD24(hi)CD38- memory B cells and are able to suppress CD4+ T-cell proliferation and IFN gamma and TNF alpha-production. In subjects with RRMS, CD19+CD24(hi)CD38(hi)transitional B cells produce significantly less IL-10 and to fail to suppress effector T-cell function. Conclusion: CD19+CD24(hi)CD38(hi)transitional B cells physiologically represent the most potent regulatory B-cell subset and are functionally defective in patients with RRMS, an abnormality that may contribute to the immune pathological process.