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Journal

Impaired suppressive capacity of activation–induced regulatory B cells in Systemic Lupus Erythematosus

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Published:25th Mar 2020

Objective:

B–cells with immunoregulatory properties have been described in mice (Breg) but their role in control of human immune responses is ill defined. We recently identified a population of human activated FSChiB–cells which exhibited regulatory activity towards T–helper (Th)–cells. Our aim was to test such induced Breg (iBreg) in autoimmune disease.

Methods:

purified CD19+FSChiB–cells of patients with Systemic Lupus Erythematosus (SLE) or healthy donors (ND), activated via their B–cell receptor, were cocultured with CD3–stimulated SLE– or ND–CD4+Th–cells. 3H–Thymidine incorporation, flow cytometry and ELISA were used for proliferation, cytokine secretion and surface marker expression.

Results:

Although under costimulatory conditions FSChiSLE–B–cells supported ND–T–cell proliferation like ND–B–cells, their regulatory function was significantly diminished in B–cell suppressor–assays. Similar effects were measured when SLE–T–cells were used, confirming that SLE–T–cells were equally susceptible to iBreg signals like ND–T–cells and that SLE–iBreg defects were independent of T–cell origin. B–cell viability and expression of surface markers (CD25, CD80, B7–H1) or cytokines (IL–6, TNFα, IL–10) were comparable between both B–cell populations. There was no correlation between extent of iBreg–induced inhibition and disease activity. CD19+FSChiB–cells from another systemic autoimmune disease, Granulomatosis with Polyangiitis (GPA), exhibited no regulatory defects, suggesting that iBreg defects were SLE–specific and not a general consequence of autoimmunity or inflammation.

Conclusion:

iBreg from SLE patients but not GPA patients are less effective in control of Th–cell proliferation, supporting the findings of a skewed B–cell repertoire in SLE. The malfunctioning SLE–iBreg might allow an overstimulation of immune responses and contribute to initiation and/or perpetuation of disease.

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