BAFF overexpression increases lymphocytic infiltration in Sjögren's target tissue, but only inefficiently promotes ectopic B-cell differentiation.

Abstract

B-cell activating factor (BAFF) levels are increased in rheumatoid arthritis, lupus and primary Sjögren's syndrome (pSS). However, BAFF contribution to pathogenesis is not completely understood. In pSS, immune infiltration of the salivary and lacrimal glands leads to xerostomia and xerophtalmia. Glandular B cell hyperactivation, differentiation into germinal center (GC)-like structures and plasma cell accumulation are histopathological hallmarks that were attributed to increased BAFF. Here, we experimentally tested this hypothesis by overexpressing BAFF in a mouse model of pSS. BAFF overexpression enhanced lymphocytic infiltration and MHCII expression on B cells. Increased BAFF also induced B cell differentiation into GC B cells within the autoimmune target tissue. However, even in these conditions, GC B cells only accounted for <1% of glandular B cells, demonstrating that BAFF is not efficiently promoting ectopic GC formation in pSS and warranting further investigation of therapeutics targeting both BAFF and the related TNF-family member APRIL.

• Authors: Jian Ding, Wei Zhang, Scott Haskett, Alex Pellerin, Shanqin Xu, Britta Petersen, Luke Jandreski, Stefan Hamann, Taylor L Reynolds, Timothy S Zheng, Michael Mingueneau
• Journal: Clinical immunology (Orlando, Fla.) (Clin Immunol) Vol. 169 Pg. 69-79 (08 2016) ISSN: 1521-7035 [Electronic] United States
• PMID: 27352977 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 Elsevier Inc. All rights reserved.

Chemical References

• B-Cell Activating Factor
• Tnfsf13b protein, mouse

Topics

• Animals
• Autoimmunity (genetics, immunology)
• B-Cell Activating Factor (genetics, immunology, metabolism)
• B-Lymphocytes (immunology, metabolism, pathology)
• Cell Differentiation (genetics, immunology)
• Cells, Cultured
• Flow Cytometry
• Gene Expression Profiling (methods)
• Germinal Center (immunology, metabolism)
• Immunohistochemistry
• Lacrimal Apparatus (immunology, metabolism)
• Male
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Mice, Inbred NOD
• Oligonucleotide Array Sequence Analysis
• Sjogren's Syndrome (genetics, immunology, metabolism)
• Xerophthalmia (genetics, immunology, metabolism)
• Xerostomia (genetics, immunology, metabolism)