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

Stott, D.I., Hiepe, F., Hummel, M., Steinhauser, G., and Berek, C. (1998) Antigen-driven clonal proliferation of B cells within the target tissue of an autoimmune disease: the salivary glands of patients with Sjögren's syndrome. Journal of Clinical Investigation, 102 (5). pp. 938-946. ISSN 0021-9738 (doi:10.1172/JCI3234 )

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Publisher's URL: http://www.jci.org/cgi/reprint/102/5/938

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.

Item Type:Article
Keywords:Autoimmunity, Sjögren's syndrome, germinal center, immunoglobulin, V-gene.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Stott, Prof David
Authors: Stott, D.I., Hiepe, F., Hummel, M., Steinhauser, G., and Berek, C.
Subjects:Q Science > QR Microbiology > QR355 Virology
College/School:College of Medical Veterinary and Life Sciences
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation > Bacteriology
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation > Centre for Virus Research
Journal Name:Journal of Clinical Investigation
Publisher:Americal Society for Clinical Investigation
ISSN:0021-9738
Copyright Holders:Copyright © 1998 American Society for Clinical Investigation
First Published:First published in Journal of Clinical Investigation 102(5):938-946
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher.

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