Ectopic expression of the B cell-attracting chemokine BCA-1 (CXCL13) on endothelial cells and within lymphoid follicles contributes to the establishment of germinal center-like structures in Sjögren's syndrome.

Abstract

OBJECTIVE:

To test the hypothesis that the formation of ectopic germinal center (GC)-like structures in Sjögren's syndrome (SS) is associated with the ectopic expression of the constitutive lymphoid tissue-homing chemokines B cell-attracting chemokine 1 (BCA-1; or, CXCL13) and stromal cell-derived factor 1 (SDF-1; or, CXCL12).

METHODS:

Immunohistochemical and immunofluorescence analysis was used to determine the expression of the constitutive chemokines BCA-1 (CXCL13) and SDF-1 (CXCL12) in salivary glands from 5 SS patients and 3 non-SS patients. In addition, the expression of their respective receptors (CXCR5 and CXCR4) was examined on infiltrating lymphocytes. Human tonsil was used as a positive control for secondary lymphoid tissue.

RESULTS:

BCA-1 (CXCL13) was expressed within lymphoid aggregates in SS, which shared many structural features with GCs in tonsil. BCA-1 (CXCL13) was completely absent in control biopsy samples from patients who did not have SS. High levels of BCA-1 (CXCL13) were also found on endothelial cells in salivary glands from SS patients. Diseased SS tissue was infiltrated by CXCR5-expressing B cells which organized into GC-like clusters. In complete contrast, SDF-1 (CXCL12), a constitutive chemokine involved in leukocyte retention within lymphoid tissue, was expressed by epithelial cells in both diseased and control samples. The chemokine receptor for SDF-1, CXCR4, was expressed on T cells that accumulated in a periductal distribution in diseased tissue.

CONCLUSION:

The ectopic expression of BCA-1 (CXCL13) on endothelial cells and within GC-like structures, together with the strong expression of SDF-1 (CXCL12) on ductal epithelial cells, is a unique feature of inflamed glands in SS. By creating a local microenvironment supportive of focal B cell aggregation and differentiation, with structural features that are remarkably similar to GCs, BCA-1 (CXCL13) and SDF-1 (CXCL12) may contribute to the excessive production of high-affinity, class-switched autoantibodies and to the high incidence of B cell lymphomas classically associated with SS.

• Authors: N Amft, S J Curnow, D Scheel-Toellner, A Devadas, J Oates, J Crocker, J Hamburger, J Ainsworth, J Mathews, M Salmon, S J Bowman, C D Buckley
• Journal: Arthritis and rheumatism (Arthritis Rheum) Vol. 44 Issue 11 Pg. 2633-41 (Nov 2001) ISSN: 0004-3591 [Print] United States
• PMID: 11710719 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CXCL12 protein, human
• CXCL13 protein, human
• CXCR5 protein, human
• Chemokine CXCL12
• Chemokine CXCL13
• Chemokines, CXC
• Receptors, CXCR4
• Receptors, CXCR5
• Receptors, Chemokine
• Receptors, Cytokine

Topics

• B-Lymphocytes (metabolism)
• Chemokine CXCL12
• Chemokine CXCL13
• Chemokines, CXC (analysis, biosynthesis)
• Endothelium, Lymphatic (metabolism, pathology)
• Fluorescent Antibody Technique, Indirect
• Germinal Center (metabolism, pathology)
• Humans
• Immunohistochemistry
• Palatine Tonsil (metabolism, pathology)
• Parotid Gland (metabolism, pathology)
• Receptors, CXCR4 (biosynthesis)
• Receptors, CXCR5
• Receptors, Chemokine
• Receptors, Cytokine (biosynthesis)
• Salivary Glands, Minor (metabolism, pathology)
• Sjogren's Syndrome (metabolism, pathology)
• Tonsillitis (metabolism, pathology)