Defective CD19+CD24^hiCD38^hi transitional B-cell function in patients with relapsing-remitting MS

Area of Science:

• Immunology
• Neuroimmunology
• Cellular Immunology

Background:

• Multiple sclerosis (MS) involves central nervous system (CNS) inflammation with T and B cell infiltration.
• Dysfunctional immune regulation and cytokine production characterize MS.
• Interleukin-10 (IL-10)-producing transitional B cells are known to suppress T cell activity and are implicated in autoimmune diseases.

Purpose of the Study:

• To investigate the hypothesis that transitional B-cell-dependent immune regulation is impaired in MS.
• To compare the function of transitional B cells in healthy individuals versus patients with relapsing-remitting multiple sclerosis (RRMS).

Main Methods:

• Peripheral blood samples were collected from 62 healthy donors and 21 RRMS patients.
• Flow cytometry was used to quantify IL-10-producing B cells, interferon-gamma (IFNγ) and tumor necrosis factor-alpha (TNFα)-producing T cells, and proliferating T cells.

Main Results:

• In healthy individuals, CD19+CD24^hiCD38^hi transitional B cells produced higher levels of IL-10 and effectively suppressed CD4+ T-cell proliferation and cytokine production (IFNγ, TNFα).
• In RRMS patients, these transitional B cells produced significantly less IL-10 and failed to suppress effector T-cell responses.

Conclusions:

• CD19+CD24^hiCD38^hi transitional B cells are the most potent regulatory B-cell subset.
• Functional defects in these regulatory B cells are present in RRMS patients.
• This B-cell dysfunction may contribute to the underlying immune pathology of multiple sclerosis.