title: Reduced non-switched memory B cell subsets cause imbalance in B cell repertoire in systemic sclerosis.
abstract: OBJECTIVE
  Analysis of peripheral blood B lymphocytes in patients with systemic sclerosis (SSc) has provided evidence for specific alterations in naive and memory B cell balance. However, memory B cell subsets in SSc have not been thoroughly investigated. This study sought to identify phenotypic abnormalities and activation markers in peripheral blood memory B cells in SSc subtypes.
  
  
  METHODS
  Blood samples were obtained from 28 SSc patients with early form of disease (9 limited (lcSSc), 19 diffuse cutaneous SSc (dcSSc)) and 15 healthy controls. After magnetic bead separation of CD19+ B cells, multiparametric flow cytometry was performed and CD19+CD27- IgD+ naive, CD19+CD27+ memory, CD19+CD27+IgD+ non-switched memory CD19+CD27+IgD- switched memory, CD19+CD27-IgD- double negative (DN) memory, CD80+ or CD95+ activated cells were identified.
  
  
  RESULTS
  The proportion of naive B cells was higher (p=0.046) in SSc than in controls, with a decreased percentage of memory (p=0.018), especially non-switched memory B cells (p=0.015). The dcSSc patients had a significantly higher frequency of switched memory and DN memory B cells compared to lcSSc patients (p=0.025 and p=0.031). Percentage of CD95+CD27+ memory and CD95+ DN memory B cells was also significantly elevated in dcSSc compared to lcSSc patients (p=0.038 and p=0.045).
  
  
  CONCLUSIONS
  We conclude that the decreased proportion of memory B cells in SSc is due to reduction of non- switched memory B cells, resulting in an imbalance between the tolerogenic and activated memory B cell types. Elevated switched and activated CD95+ DN memory B cells may serve as a biomarker for dcSSc and can have a pathogenic potential by cytokine and autoantibody production.
authors.affiliation: Department of Immunology and Biotechnology, University of Pécs, Clinical Center, Pécs, Hungary.
authors.forename: Diána
authors.initials: D
authors.lastname: Simon
authors.affiliation: Department of Immunology and Biotechnology, University of Pécs, Clinical Center, Pécs, Hungary.
authors.forename: Péter
authors.initials: P
authors.lastname: Balogh
authors.affiliation: Department of Immunology and Biotechnology, University of Pécs, Clinical Center, Pécs, Hungary.
authors.forename: András
authors.initials: A
authors.lastname: Bognár
authors.affiliation: Department of Immunology and Biotechnology, University of Pécs, Clinical Center, Pécs, Hungary.
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Kellermayer
authors.affiliation: Department of Immunology and Biotechnology, University of Pécs, Clinical Center, Pécs, Hungary.
authors.forename: Péter
authors.initials: P
authors.lastname: Engelmann
authors.affiliation: Department of Immunology and Biotechnology, University of Pécs, Clinical Center, Pécs, Hungary.
authors.forename: Péter
authors.initials: P
authors.lastname: Németh
authors.affiliation: Institute of Bioanalysis, University of Pécs, Medical School, Pécs, Hungary.
authors.forename: Nelli
authors.initials: N
authors.lastname: Farkas
authors.affiliation: Department of Rheumatology and Immunology, University of Pécs, Clinical Center, Pécs, Hungary.
authors.forename: Tünde
authors.initials: T
authors.lastname: Minier
authors.affiliation: Department of Rheumatology and Immunology, University of Pécs, Clinical Center, Pécs, Hungary.
authors.forename: Veronika
authors.initials: V
authors.lastname: Lóránd
authors.affiliation: Department of Rheumatology and Immunology, University of Pécs, Clinical Center, Pécs, Hungary.
authors.forename: László
authors.initials: L
authors.lastname: Czirják
authors.affiliation: Department of Immunology and Biotechnology, University of Pécs, Clinical Center, Pécs, Hungary. berki.timea@pte.hu.
authors.forename: Tímea
authors.initials: T
authors.lastname: Berki
mesh_terms: D000328:Adult; D000368:Aged; D018941:Antigens, CD19 / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D002469:Cell Separation / Q000379:methods; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping / Q000379:methods; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D045743:Scleroderma, Diffuse / Q000097:blood / Q000175:diagnosis / Q000276:immunology*; D012595:Scleroderma, Systemic / Q000097:blood / Q000175:diagnosis / Q000276:immunology*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000276:immunology / Q000378:metabolism; D019014:fas Receptor / Q000276:immunology / Q000378:metabolism
chemical_list: D018941:Antigens, CD19; D015415:Biomarkers; C000604811:CD19 molecule, human; C491901:FAS protein, human; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D019014:fas Receptor