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Publication Detail
Altered lipid raft-associated proximal signaling and translocation of CD45 tyrosine phosphatase in B lymphocytes from patients with systemic lupus erythematosus
  • Publication Type:
    Journal article
  • Publication Sub Type:
    Journal Article
  • Authors:
    Flores-Borja F, Kabouridis PS, Jury EC, Isenberg DA, Mageed RA
  • Publication date:
    01/01/2007
  • Pagination:
    291, 302
  • Journal:
    Arthritis and Rheumatism
  • Volume:
    56
  • Issue:
    1
  • Status:
    Published
  • Print ISSN:
    0004-3591
Abstract
Objective. B lymphocytes from patients with systemic lupus erythematosus (SLE) exhibit defective intracellular signaling, hyperactivity, and autoantibody production. Recent evidence indicates a reduced expression of Lyn Idnase, a negative regulator of B cell signaling, and reduced translocation of Lyn into membrane signaling domains in SLE. The present study was undertaken to investigate the causes of this altered regulation of Lyn by assessing the expression levels of regulatory molecules and their translocation into the signaling domains of SLE B lymphocytes. Methods. Blood was obtained from 48 patients with SLE and 28 healthy controls for the assessment of B lymphocytes. Levels and intracellular distribution of Lyn, CD45, COOH-terminal Src kinase (Csk), and c-Cbl were studied by Western blotting, confocal microscopy, and flow cytometry. The kinetics of signaling molecule translocation to the B cell receptor (BCR)-antigen synapse were investigated by confocal microscopy. Results. A profound alteration in the expression and translocation of regulatory signaling molecules in membrane domains of B cells from patients with SLE was observed. B lymphocytes from SLE patients, but not those from healthy controls, expressed a low molecular weight isoform of CD45 in Iipid raft signaling microdomains. Kinetic studies revealed that translocation of Lyn, CD45, Csk, and c-Cbl led to increased recruitment and retention of Lyn and CD45 in the BCR-aetigen synapse in SLE B cells. Conclusion. The results provide evidence of altered expression and translocation/interaction of Idnases and phosphatases in membrane signaling mi-crodomains of B cells from patients with SLE. Altered translocation of CD45 correlated with reduced expression of Lyn, indicating that Lyn is a key molecule in the regulation of BCR-mediated signaling. © 2007, American College of Rheumatology.
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