| Autor: |
Nele, Gao, Julia, Dresel, Volker, Eckstein, Rimma, Gellert, Hannah, Störch, Ram K C, Venigalla, Vedat, Schwenger, Regina, Max, Norbert, Blank, Hanns-Martin, Lorenz, Theresa, Tretter |
| Rok vydání: |
2013 |
| Předmět: |
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| Zdroj: |
Arthritisrheumatology (Hoboken, N.J.). 66(10) |
| ISSN: |
2326-5205 |
| Popis: |
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.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.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.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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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