Open AccessEctopic 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
Author(s) -
Amft Nicole,
Curnow S. John,
ScheelToellner Dagmar,
Devadas Ash,
Oates Jane,
Crocker John,
Hamburger John,
Ainsworth John,
Mathews John,
Salmon Mike,
Bowman Simon J.,
Buckley Christopher D.
Publication year - 2001
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/1529-0131(200111)44:11<2633::aid-art443>3.0.co;2-9
Subject(s) - cxcl13 , germinal center , cxcr5 , chemokine , b cell , stromal cell derived factor 1 , tonsil , chemokine receptor , biology , stromal cell , cxcl14 , cc chemokine receptors , pathology , cxcr4 , immunology , antibody , cancer research , medicine , immune system
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.