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. 2004 Nov;24(6):600-11. doi: 10.1007/s10875-004-6240-7.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Apoptosis*
  • B-Cell Activating Factor
  • B-Lymphocytes / pathology*
  • Biomarkers / analysis
  • Blood Cells
  • Case-Control Studies
  • Female
  • Humans
  • Hypergammaglobulinemia
  • Immunoglobulin G / biosynthesis
  • Laser Scanning Cytometry
  • Male
  • Membrane Proteins / blood
  • Membrane Proteins / physiology
  • Middle Aged
  • Sjogren's Syndrome / immunology
  • Sjogren's Syndrome / pathology*
  • Tumor Necrosis Factor-alpha / physiology

Substances

  • B-Cell Activating Factor
  • Biomarkers
  • Immunoglobulin G
  • Membrane Proteins
  • TNFSF13B protein, human
  • Tumor Necrosis Factor-alpha