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. (doi: 10.1172/JCI3234)

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: Articles
• Keywords: Autoimmunity, Sjögren's syndrome, germinal center, immunoglobulin, V-gene.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Stott I, Professor 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 > School of Infection & Immunity
• 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.