Analysis of IgVH-specific, CXCR4-specific and CXR5-specific mRNA transcripts in individual peripheral blood B cells of patients with primary Sjögren's syndrome and normal healthy subjects

Background

Disturbances in peripheral B-cell homeostasis have been found to be characteristic of primary Sjögren's syndrome (pSS). Abnormal chemokine receptor expression has been proposed to be involved in the pathogenesis of autoimmune diseases.

Objective

This study aimed to further delineate disturbances in peripheral CD27^- naive and CD27⁺ memory B cells and their expression of chemokine receptors in pSS.

Methods

Isotype-specific immunoglobulin heavy chain (IgH) transcripts as well as chemokine receptor (CXCR4 and CXCR5) specific mRNA transcripts were analyzed in single-sorted CD19⁺D27^- naïve and CD19⁺CD27⁺ memory B cells from pSS patients and normal healthy subjects (NHS).

Results

A significantly higher frequency of B cells coexpressing μ, α, and/or γ chain transcripts were found in pSS patients compared with controls (58.0% versus 14.3%, P < 0.0001). Contrasting the findings in NHS, peripheral memory B cells in pSS patients were characterized by heavily mutated IgV_H transcripts (mutational frequency, 8.6% versus 4.4%; P < 0.0001). Notably, this included significantly enhanced mutational frequencies of Cμ-transcripts (9.6% in pSS versus 2.5% in NHS, P < 0.0001). A CD27^- memory-type B-cell subpopulation expressing mutated Cμ-transcripts was exclusively found in pSS patients. Moreover, a significantly enhanced frequency of CXCR4-mRNA-positive CD27^- naive B cells was found in pSS patients when compared with NHS (36.0% versus 18.1%, P < 0.0001).

Conclusions

Altogether, B-cell hyperactivity and abnormalities in peripheral B-cell memory are characteristic of patients with pSS. Differential expression of chemokine receptors appear to be involved in disturbances of peripheral B-cell homoestasis in pSS.