Impaired suppressive capacity of activation-induced regulatory B cells in systemic lupus erythematosus

• Verfasst von: Gao, Nele Xian-Tai [VerfasserIn]
• Verfasst von: Dresel, Julia [VerfasserIn]
• Verfasst von: Eckstein, Volker [VerfasserIn]
• Verfasst von: Gellert, Rimma [VerfasserIn]
• Verfasst von: Ostermann, Hannah [VerfasserIn]
• Verfasst von: Venigalla, Ram Kumar Chowdary [VerfasserIn]
• Verfasst von: Schwenger, Vedat [VerfasserIn]
• Verfasst von: Max, Regina [VerfasserIn]
• Verfasst von: Blank, Norbert [VerfasserIn]
• Verfasst von: Lorenz, Hanns-Martin [VerfasserIn]
• Verfasst von: Tretter, Theresa [VerfasserIn]
• Titel: Impaired suppressive capacity of activation-induced regulatory B cells in systemic lupus erythematosus
• Verf.angabe: Nele Gao, Julia Dresel, Volker Eckstein, Rimma Gellert, Hannah Störch, Ram K. C. Venigalla, Vedat Schwenger, Regina Max, Norbert Blank, Hanns-Martin Lorenz, and Theresa Tretter
• E-Jahr: 2014
• Jahr: 18 June 2014
• Umfang: 13 S.
• Fussnoten: Gesehen am 21.07.2020
• Titel Quelle: Enthalten in: Arthritis & rheumatology
• Ort Quelle: Hoboken, NJ : Wiley, 2014
• Jahr Quelle: 2014
• Band/Heft Quelle: 66(2014), 10, Seite 2849-2861
• ISSN Quelle: 2326-5205
• DOI: doi:10.1002/art.38742
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1725204835

Abstract

Objective 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 FSChigh 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+FSChigh 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. 3H-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, FSChigh 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+FSChigh 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.