Association of BAFF/BLyS overexpression and altered B cell differentiation with Sjögren's syndrome.

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Serval ID
serval:BIB_5CB80E5FBAFB
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Association of BAFF/BLyS overexpression and altered B cell differentiation with Sjögren's syndrome.
Journal
Journal of Clinical Investigation
Author(s)
Groom J., Kalled S.L., Cutler A.H., Olson C., Woodcock S.A., Schneider P., Tschopp J., Cachero T.G., Batten M., Wheway J., Mauri D., Cavill D., Gordon T.P., Mackay C.R., Mackay F.
ISSN
0021-9738 (Print)
ISSN-L
0021-9738
Publication state
Published
Issued date
2002
Volume
109
Number
1
Pages
59-68
Language
english
Abstract
BAFF (BLyS, TALL-1, THANK, zTNF4) is a member of the TNF superfamily that specifically regulates B lymphocyte proliferation and survival. Mice transgenic (Tg) for BAFF develop an autoimmune condition similar to systemic lupus erythematosus. We now demonstrate that BAFF Tg mice, as they age, develop a secondary pathology reminiscent of Sjögren's syndrome (SS), which is manifested by severe sialadenitis, decreased saliva production, and destruction of submaxillary glands. In humans, SS also correlates with elevated levels of circulating BAFF, as well as a dramatic upregulation of BAFF expression in inflamed salivary glands. A likely explanation for disease in BAFF Tg mice is excessive survival signals to autoreactive B cells, possibly as they pass through a critical tolerance checkpoint while maturing in the spleen. The marginal zone (MZ) B cell compartment, one of the enlarged B cell subsets in the spleen of BAFF Tg mice, is a potential reservoir of autoreactive B cells. Interestingly, B cells with an MZ-like phenotype infiltrate the salivary glands of BAFF Tg mice, suggesting that cells of this compartment potentially participate in tissue damage in SS and possibly other autoimmune diseases. We conclude that altered B cell differentiation and tolerance induced by excess BAFF may be central to SS pathogenesis.
Keywords
Age Factors, Animals, Autoimmunity, B-Cell Activating Factor, B-Lymphocytes/immunology, B-Lymphocytes/pathology, Cell Differentiation/genetics, Cell Differentiation/immunology, Disease Models, Animal, Gene Expression, Humans, Immune Tolerance, Membrane Proteins/blood, Membrane Proteins/genetics, Mice, Mice, Inbred C57BL, Mice, Transgenic, Saliva/secretion, Sjogren's Syndrome/etiology, Sjogren's Syndrome/genetics, Species Specificity, Submandibular Gland/pathology, Tumor Necrosis Factor-alpha/genetics, Tumor Necrosis Factor-alpha/immunology
Pubmed
Web of science
Open Access
Yes
Create date
24/01/2008 16:19
Last modification date
18/01/2020 7:17
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