Defective CD19+CD24 hi CD38 hi transitional B-cell function in patients with relapsing-remitting MS

Abstract

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^hiCD38^hi transitional B cells producing interleukin (IL)-10 have been shown to suppress interferon-γ (IFNγ) and tumour necrosis factor-α (TNFα) 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, IFNγ and TNFα-producing T cells and proliferating T cells were quantified by flow cytometry.

Results:

In healthy individuals, CD19+CD24^hiCD38^hi transitional B cells produce more IL-10 than CD19+CD24+CD38+ naive and CD19+CD24^hiCD38− memory B cells and are able to suppress CD4+ T-cell proliferation and IFNγ and TNFα-production. In subjects with RRMS, CD19+CD24^hiCD38^hi transitional B cells produce significantly less IL-10 and to fail to suppress effector T-cell function.

Conclusion:

CD19+CD24^hiCD38^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.

Keywords

Multiple sclerosis B cells immune regulatory cells IL-10 CD40/CD40L pathway transitional B cells

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