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Research Article Free access | 10.1172/JCI3234

Antigen-driven clonal proliferation of B cells within the target tissue of an autoimmune disease. The salivary glands of patients with Sjögren's syndrome.

D I Stott, F Hiepe, M Hummel, G Steinhauser, and C Berek

University Department of Immunology, Western Infirmary, Glasgow G11 6NT, Scotland, United Kingdom. d.i.stott@clinmed.gla.ac.uk

Find articles by Stott, D. in: PubMed | Google Scholar

University Department of Immunology, Western Infirmary, Glasgow G11 6NT, Scotland, United Kingdom. d.i.stott@clinmed.gla.ac.uk

Find articles by Hiepe, F. in: PubMed | Google Scholar

University Department of Immunology, Western Infirmary, Glasgow G11 6NT, Scotland, United Kingdom. d.i.stott@clinmed.gla.ac.uk

Find articles by Hummel, M. in: PubMed | Google Scholar

University Department of Immunology, Western Infirmary, Glasgow G11 6NT, Scotland, United Kingdom. d.i.stott@clinmed.gla.ac.uk

Find articles by Steinhauser, G. in: PubMed | Google Scholar

University Department of Immunology, Western Infirmary, Glasgow G11 6NT, Scotland, United Kingdom. d.i.stott@clinmed.gla.ac.uk

Find articles by Berek, C. in: PubMed | Google Scholar

Published September 1, 1998 - More info

Published in Volume 102, Issue 5 on September 1, 1998
J Clin Invest. 1998;102(5):938–946. https://doi.org/10.1172/JCI3234.
© 1998 The American Society for Clinical Investigation
Published September 1, 1998 - Version history
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Abstract

Structures resembling germinal centers are seen in the salivary glands of patients with Sjögren's syndrome, but it is not known whether the microenvironment of these cell clusters is sufficient for the induction of a germinal center response. Therefore, we cloned and sequenced rearranged Ig V genes expressed by B cells isolated from sections of labial salivary gland biopsies from two Sjögren's syndrome patients. Rearranged V genes from B cells within one cell cluster were polyclonal and most had few somatic mutations. Two adjacent clusters from another patient each contained one dominant B cell clone expressing hypermutated V genes. None of the rearranged V genes was found in both clusters, suggesting that cells are unable to migrate out into the surrounding tissue and seed new clusters. The ratios of replacement to silent mutations in the framework and complementarity determining regions suggest antigen selection of high-affinity mutants. These results show that an antigen-driven, germinal center-type B cell response is taking place within the salivary glands of Sjögren's syndrome patients. In view of the recent demonstration of a germinal center response within the rheumatoid synovial membrane and the existence of similar structures in the target tissues of other autoimmune diseases, we propose that germinal center- type responses can be induced in the nonlymphoid target tissues of a variety of autoimmune diseases.

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