• Arthritis and rheumatism · Jul 2005

    Dysregulation of chemokine receptor expression and function by B cells of patients with primary Sjögren's syndrome.

    • Arne Hansen, Karin Reiter, Till Ziprian, Annett Jacobi, Andreas Hoffmann, Mirko Gosemann, Jürgen Scholze, Peter E Lipsky, and Thomas Dörner.
    • Department of Medicine, Outpatient Department, Charité University Hospital, Berlin, Germany. arne.hansen@charite.de
    • Arthritis Rheum. 2005 Jul 1; 52 (7): 2109-19.

    ObjectiveTo assess whether abnormal chemokine receptor expression and/or abnormal responsiveness to the cognate ligands might underlie some of the disturbances in B cell homeostasis characteristic of primary Sjögren's syndrome (SS).MethodsChemokine receptor expression by CD27- naive and CD27+ memory B cells from patients with primary SS and healthy control subjects was analyzed using flow cytometry, single-cell reverse transcriptase-polymerase chain reaction (RT-PCR), and migration assays.ResultsIn contrast to healthy subjects, significantly higher expression of both surface CXCR4 and CXCR4 messenger RNA (mRNA) was seen in peripheral blood B cells from patients with primary SS. These differences were most prominent in CD27- naive B cells (P < or = 0.0006). In addition, significantly higher frequencies of CD27- naive B cells from patients with primary SS expressed mRNA for the inhibitory regulator of G protein signaling 13 (P = 0.001). Expression of CXCR5 by peripheral CD27+ memory B cells was moderately diminished in patients with primary SS compared with healthy controls (P = 0.038). No significant differences were noted in the expression of CXCR3, CCR6, CCR7, and CCR9 between B cells from healthy controls and those from patients with primary SS. Transmigration assays of blood B cells from patients with primary SS and healthy controls showed comparable responses of CD27- naive B cells but significantly diminished responses of activated primary SS CD27+ memory B cells to the ligands of CXCR4 and CXCR5, CXCL12 (P = 0.032), and CXCL13 (B lymphocyte chemoattractant; B cell-attracting chemokine 1; P = 0.018), respectively, when compared with those from healthy controls. Finally, compared with controls, peripheral reduction but glandular accumulation of CXCR4+,CXCR5+,CD27+ memory B cells was identified in patients with primary SS.ConclusionIn primary SS, overexpression of CXCR4 by circulating blood B cells does not translate into enhanced migratory response to the cognate ligand, CXCL12. This migratory response may be modulated by intracellular regulators. Retention of CXCR4+,CXCR5+, CD27+ memory B cells in the inflamed glands seems to contribute to diminished peripheral CD27+ memory B cells in primary SS.

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