title: Programmed cell death of peripheral blood B cells determined by laser scanning cytometry in Sjögren's syndrome with a special emphasis on BAFF.
abstract: Functionally impaired B cells play an important role in the pathogenesis of Sjögren's syndrome (SS). The aim of the study was to investigate the apoptosis susceptibility of peripheral blood B cells from patients with SS and the impact of B cell activating factor (BAFF) on the apoptosis capability of these cells in correlation with IgG production. Peripheral blood B cells were isolated and stained for apoptosis markers (Bax, Bcl-2) and members of the TNF-R superfamily, CD95 and CD40. The apoptosis frequency of cells bearing these markers were assessed. Also, the apoptosis capability of cultured B-lymphocytes was investigated in medium alone, with anti-CD95 or with soluble BAFF. Quantitative ELISA was performed to detect plasma levels of sBAFF. Furthermore, the level of circulating B-cell cytokines was measured. BAFF levels were compared between patients with normal and elevated IgG levels. In SS, Bcl-2 positive B cell counts were significantly higher then in controls, also in this population the apoptosis frequency was reduced. Apoptosis within Bax+ and CD40+ B cells were significantly decreased in patients. BAFF induced a significant antiapoptotic effect in SS; also this effect was clearly evident in B cells from SS with hypergammaglobulinaemia. Plasma BAFF levels were significantly higher in SS, mostly in patients with hypergammaglobulinaemia. Plasma B-cell cytokines were raised in SS. In Sjögren's syndrome B cells, a general antiapoptotic tendency might lead to prolonged B-cell survival driven at least partly by elevated levels of BAFF and supposedly by B-cell cytokines. Also, the exaggerated BAFF stimulation might lead to excessive immunoglobulin production. The B-cell apoptosis defects, the increased BAFF levels-correlating with hypergammaglobulinaemia-together with the raised B-cell cytokine levels indicates the disturbed B-cell biology in the disease.
authors.affiliation: Broegelmann Research Laboratory, The Gade Institute, University of Bergen, Bergen, Norway. peter.szodoray@gades.uib.no
authors.forename: Peter
authors.initials: P
authors.lastname: Szodoray
authors.forename: Stig
authors.initials: S
authors.lastname: Jellestad
authors.forename: Philip
authors.initials: P
authors.lastname: Alex
authors.forename: Tong
authors.initials: T
authors.lastname: Zhou
authors.forename: Patrick C
authors.initials: PC
authors.lastname: Wilson
authors.forename: Michael
authors.initials: M
authors.lastname: Centola
authors.forename: Johan G
authors.initials: JG
authors.lastname: Brun
authors.forename: Roland
authors.initials: R
authors.lastname: Jonsson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D053264:B-Cell Activating Factor; D001402:B-Lymphocytes / Q000473:pathology*; D015415:Biomarkers / Q000032:analysis; D001773:Blood Cells; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D006942:Hypergammaglobulinemia; D007074:Immunoglobulin G / Q000096:biosynthesis; D047569:Laser Scanning Cytometry; D008297:Male; D008565:Membrane Proteins / Q000097:blood / Q000502:physiology; D008875:Middle Aged; D012859:Sjogren's Syndrome / Q000276:immunology / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
chemical_list: D053264:B-Cell Activating Factor; D015415:Biomarkers; D007074:Immunoglobulin G; D008565:Membrane Proteins; C505719:TNFSF13B protein, human; D014409:Tumor Necrosis Factor-alpha