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 Sjogren's syndrome

Objective. To test the hypothesis that the formation of ectopic germinal ce nter (GC)-like structures in Sjogren'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 f actor 1 (SDF-1; or, CXCL12). Methods. Immunohistochemical and immunofluorescence analysis was used to de termine the expression of the constitutive chemokines BCA-1 (CXCL13) and SD F-1 (CXCL12) in salivary glands from 5 SS patients and 3 non-SS patients. I n addition, the expression of their respective receptors (CXCR5 and CXCR4) was examined on infiltrating lymphocytes. Human tonsil was used as a positi ve control for secondary lymphoid tissue. Results. BCA-1 (CXCL13) was expressed within lymphoid aggregates in SS, whi ch shared many structural features with GCs in tonsil. BCA-1 (CXCL13) was c ompletely absent in control biopsy samples from patients who did not have S S. High levels of BCA-1 (CXCL13) were also found on endothelial cells in sa livary glands from SS patients. Diseased SS tissue was infiltrated by CXCR5 -expressing B cells which organized into GC-like clusters. In complete cont rast, SDF-1 (CXCL12), a constitutive chemokine involved in leukocyte retent ion within lymphoid tissue, was expressed by epithelial cells in both disea sed and control samples. The chemokine receptor for SDF-1, CXCR4, was expre ssed on T cells that accumulated in a periductal distribution in diseased t issue. Conclusion. The ectopic expression of BCA-1 (CXCL13) on endothelial cells a nd 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 agg regation and differentiation, with structural features that are remarkably similar to GCs, BCA-1 (CXCL13) and SDF-1 (CXCL12) may contribute to the exc essive production of high-affinity, class-switched autoantibodies and to th e high incidence of B cell lymphomas classically associated with SS.