title: Impaired suppressive capacity of activation-induced regulatory B cells in systemic lupus erythematosus.
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 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: University of Heidelberg, Heidelberg, Germany.
authors.forename: Nele
authors.initials: N
authors.lastname: Gao
authors.forename: Julia
authors.initials: J
authors.lastname: Dresel
authors.forename: Volker
authors.initials: V
authors.lastname: Eckstein
authors.forename: Rimma
authors.initials: R
authors.lastname: Gellert
authors.forename: Hannah
authors.initials: H
authors.lastname: Störch
authors.forename: Ram K C
authors.initials: RK
authors.lastname: Venigalla
authors.forename: Vedat
authors.initials: V
authors.lastname: Schwenger
authors.forename: Regina
authors.initials: R
authors.lastname: Max
authors.forename: Norbert
authors.initials: N
authors.lastname: Blank
authors.forename: Hanns-Martin
authors.initials: HM
authors.lastname: Lorenz
authors.forename: Theresa
authors.initials: T
authors.lastname: Tretter
mesh_terms: D060151:B-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism
chemical_list: D015415:Biomarkers; D016207:Cytokines