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Programmed Cell Death of Peripheral Blood B Cells Determined by Laser Scanning Cytometry in Sjögren’s Syndrome with a Special Emphasis on BAFF

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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.

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Authors and Affiliations

  1. Broegelmann Research Laboratory, The Gade Institute, University of Bergen, Bergen, Norway

    PETER SZODORAY, STIG JELLESTAD & ROLAND JONSSON

  2. Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma

    PETER SZODORAY, PHILIP ALEX, PATRICK C. WILSON & MICHAEL CENTOLA

  3. Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama

    TONG ZHOU

  4. Department of Rheumatology, Haukeland University Hospital, University of Bergen, Norway

    JOHAN G. BRUN

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  1. PETER SZODORAY
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  2. STIG JELLESTAD
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  3. PHILIP ALEX
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  4. TONG ZHOU
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Correspondence to PETER SZODORAY.

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SZODORAY, P., JELLESTAD, S., ALEX, P. et al. Programmed Cell Death of Peripheral Blood B Cells Determined by Laser Scanning Cytometry in Sjögren’s Syndrome with a Special Emphasis on BAFF. J Clin Immunol 24, 600–611 (2004). https://doi.org/10.1007/s10875-004-6240-7

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  • DOI: https://doi.org/10.1007/s10875-004-6240-7

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