Open AccessDysregulation of chemokine receptor expression and function by B cells of patients with primary Sjögren's syndrome
Author(s) -
Hansen Arne,
Reiter Karin,
Ziprian Till,
Jacobi Annett,
Hoffmann Andreas,
Gosemann Mirko,
Scholze Jürgen,
Lipsky Peter E.,
Dörner Thomas
Publication year - 2005
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/art.21129
Subject(s) - cxcl13 , c c chemokine receptor type 7 , chemokine receptor , cxcr5 , b cell , c c chemokine receptor type 6 , chemokine , cc chemokine receptors , flow cytometry , receptor , cxcr4 , xcl2 , ccl17 , immunology , ccl13 , cxcr3 , medicine , biology , antibody
Abstract Objective To 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). Methods Chemokine 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. Results In 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 ≤ 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. Conclusion In 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.