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


CONCLUSIONS
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.
Salomonsson
Stina
S
Karolinska Institutet, Stockholm, Sweden.
Jonsson
Malin V
MV
Skarstein
Kathrine
K
Brokstad
Karl A
KA
Hjelmström
Peter
P
Wahren-Herlenius
Marie
M
Jonsson
Roland
R
D017209:Apoptosis; D001402:B-Lymphocytes / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers; D002452:Cell Count; D002828:Choristoma; D020566:Dendritic Cells, Follicular / Q000378:metabolism / Q000473:pathology; D004729:Endothelium, Lymphatic / Q000378:metabolism / Q000473:pathology; D018858:Germinal Center / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007124:Immunoenzyme Techniques; D020287:In Situ Nick-End Labeling; D008875:Middle Aged; D012466:Salivary Gland Diseases / Q000378:metabolism / Q000473:pathology*; D012470:Salivary Glands, Minor / Q000378:metabolism / Q000473:pathology*; D012859:Sjogren's Syndrome / Q000378:metabolism / Q000473:pathology*; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology
D015415:Biomarkers