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

Arthritis Rheum. 2001 Nov;44(11):2633-41. doi: 10.1002/1529-0131(200111)44:11<2633::aid-art443>;2-9.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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


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