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

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

Rituximab in primary Sjögren's syndrome: a ten-year journey

“…37,38 These interactions are involved in B-cell deregulation, such as the preferential migration of CXCR4 and CXCR5 expressing CD27 þ memory B cells, the homing of CCR7-expressing naive B cells into the inflamed salivary glands, and the development of ectopic GC-like structures as well as the peripheral B-cell abnormalities. [39][40][41] In this setting, we observed a consistent reduction at mRNA levels of CXCR4 and CXCR5, associated with a parallel increase of the CXCL12 and CXCL13 mRNAs, following anti-CD20 therapy. Although Lta and Ltb were markedly reduced by RTX, BAFF was not affected by the biological treatment.…”

Is minor salivary gland biopsy more than a diagnostic tool in primary Sjo¨gren׳s syndrome? Association between clinical, histopathological, and molecular features: A retrospective study

“…Furthermore, when compared with the inflammatory process of non-specific sialadenitis, salivary glands of patients with pSS have been found to express a unique profile of cytokines, including a striking overexpression of CXCL13 and, to a lesser degree, CXCL12 [44][45][46][47][48]. Furthermore, CXCL12-CXCR4 and CXCL13-CXCR5 interactions have been suggested to be involved in B-cell deregulation, preferential migration of CXCR4-and CXCR5-expressing CD27þ memory B-cells into the inflamed salivary glands, the development of ectopic GC-like structures as well as the peripheral B-cell abnormalities [49,50].…”

Altered expression of the receptor-ligand pair CXCR5/CXCL13 in B cells during chronic HIV-1 infection

“…There were no significant differences in the expression of CD19 between patients and controls, and the expression of chemokine receptors on cells from the healthy controls was similar to previous findings. 30 The CXCR5 expression on B cells was significantly reduced comparing HIV-1-infected patients with healthy controls (MFI 111 [range, vs 169 [range, 14-286]; P ϭ .01; Figure 1B left panel). CXCR4 expression on B cells was similar in HIV-1-infected subjects compared with healthy controls (MFI 64 [range, vs 70 [range, 14-220]; P Ͼ .05; Figure 1C left panel).…”

“…There were no significant differences in the expression of CD19 between patients and controls, and the expression of chemokine receptors on cells from the healthy controls was similar to previous findings. 30 The CXCR5 expression on B cells was significantly reduced comparing HIV-1-infected patients with healthy controls (MFI 111 [range, To clarify whether CD4 ϩ T-cell count correlates to the expression of chemokine receptors, patients were divided into 2 groups depending on the CD4 ϩ T-cell counts. The expression of CXCR5 in HIV-1-infected patients (n ϭ 18) with a CD4 ϩ T-cell count less than 350 cells/L was decreased compared with patients (n ϭ 12) with a CD4 ϩ T-cell count more than 350 cells/L (P ϭ .04; Figure 1B right panel).…”