In:
Arthritis & Rheumatology, Wiley, Vol. 66, No. 10 ( 2014-10), p. 2849-2861
Abstract:
B cells with immunoregulatory properties (Breg cells) have been described in mice, but their role in the control of human immune responses is not well defined. We recently identified a human population of activated FSC high B cells that exhibited regulatory activity toward T helper cells. The aim of the present study was to test such induced Breg (iBreg) cells in patients with autoimmune disease. Methods Purified CD19+FSC high B cells derived from patients with systemic lupus erythematosus (SLE) or from healthy donors, which were activated via their B cell receptor, were cocultured with CD3‐stimulated CD4+ T helper cells from SLE patients or healthy donors. 3 H‐thymidine incorporation, flow cytometry, and enzyme‐linked immunosorbent assay (ELISA) were used to analyze proliferation, cytokine secretion, and surface marker expression. Results Although under costimulatory conditions, FSC high SLE B cells supported the proliferation of healthy donor T cells to a similar extent as donor B cells, their regulatory function was significantly diminished in B cell suppressor assays. Similar effects were seen when SLE T cells were used, confirming that SLE T cells were equally susceptible to iBreg cell signals as healthy donor T cells and that SLE iBreg cell defects were independent of T cell origin. B cell viability and expression of surface markers (CD25, CD80, and B7‐H1) or cytokines (interleukin‐6 [IL‐6], tumor necrosis factor α, and IL‐10) were comparable in the two B cell populations. There was no correlation between the extent of iBreg cell–induced inhibition and disease activity. CD19+FSC high B cells from patients with another systemic autoimmune disease, granulomatosis with polyangiitis (Wegener's) (GPA), exhibited no regulatory defects, which suggests that the iBreg cell defects were SLE‐specific and not a general consequence of autoimmunity or inflammation. Conclusion Induced Breg cells from SLE patients, but not GPA patients, are less effective in the control of T helper cell proliferation, which supports the reported skewed B cell repertoire in SLE. The malfunctioning SLE iBreg cells might allow the overstimulation of immune responses and contribute to the initiation and/or perpetuation of disease.
Type of Medium:
Online Resource
ISSN:
2326-5191
,
2326-5205
Language:
English
Publisher:
Wiley
Publication Date:
2014
detail.hit.zdb_id:
2754614-7
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