Cellular basis of ectopic germinal center formation and autoantibody production in the target organ of patients with Sjögren's syndrome

Arthritis Rheum. 2003 Nov;48(11):3187-201. doi: 10.1002/art.11311.


Objective: To investigate functional properties of the germinal center (GC)-like structures observed in salivary glands of patients with Sjögren's syndrome (SS) and to determine the frequency with which such structures develop.

Methods: Hematoxylin and eosin-stained sections from 165 minor salivary gland biopsy samples were screened for GC-like structures. Expression of markers for GCs (CD3, CD20, Ki-67, CD35, CD31), adhesion molecules (intercellular adhesion molecule 1, lymphocyte function-associated antigen 1, vascular cell adhesion molecule 1, very late activation antigen 4), chemokines (CXCL13, CCL21, CXCL12), and production of autoantibodies (anti-Ro/SSA and anti-La/SSB) was investigated by immunohistochemistry. Apoptosis was investigated by TUNEL staining.

Results: GC-like structures were observed in 28 of 165 patients (17%). When GCs were defined as T and B cell aggregates with proliferating cells with a network of follicular dendritic cells and activated endothelial cells, such microenvironments were found in all patients in whom structures with GC-like morphology were observed. The defined microenvironments were not found in patients without apparent GC-like structures. The GCs formed within the target tissue showed functional features with production of autoantibodies (anti-Ro/SSA and anti-La/SSB) and apoptotic events (by TUNEL staining), and the local production of anti-Ro/SSA and anti-La/SSB autoantibodies was significantly increased (P = 0.04) in patients with GC development.

Conclusion: Lymphoid neogenesis and functional ectopic GC formation take place in salivary glands of a subset of patients with SS. Our data suggest that the ectopic secondary lymphoid follicles contain all elements needed for driving the autoimmune response. Our findings underscore a key role for the target organ in recruitment of inflammatory cells and propagation of the disease process.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • B-Lymphocytes / metabolism
  • B-Lymphocytes / pathology
  • Biomarkers
  • Cell Count
  • Choristoma*
  • Dendritic Cells, Follicular / metabolism
  • Dendritic Cells, Follicular / pathology
  • Endothelium, Lymphatic / metabolism
  • Endothelium, Lymphatic / pathology
  • Germinal Center / metabolism
  • Germinal Center / pathology*
  • Humans
  • Immunoenzyme Techniques
  • In Situ Nick-End Labeling
  • Middle Aged
  • Salivary Gland Diseases / metabolism
  • Salivary Gland Diseases / pathology*
  • Salivary Glands, Minor / metabolism
  • Salivary Glands, Minor / pathology*
  • Sjogren's Syndrome / metabolism
  • Sjogren's Syndrome / pathology*
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / pathology


  • Biomarkers