title: 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.affiliation: Immunology Research, Biogen, 115 Broadway, Cambridge, MA 02142, United States.
authors.forename: Jian
authors.initials: J
authors.lastname: Ding
authors.affiliation: Immunology Research, Biogen, 115 Broadway, Cambridge, MA 02142, United States.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Immunology Research, Biogen, 115 Broadway, Cambridge, MA 02142, United States.
authors.forename: Scott
authors.initials: S
authors.lastname: Haskett
authors.affiliation: Immunology Research, Biogen, 115 Broadway, Cambridge, MA 02142, United States.
authors.forename: Alex
authors.initials: A
authors.lastname: Pellerin
authors.affiliation: Immunology Research, Biogen, 115 Broadway, Cambridge, MA 02142, United States.
authors.forename: Shanqin
authors.initials: S
authors.lastname: Xu
authors.affiliation: Immunology Research, Biogen, 115 Broadway, Cambridge, MA 02142, United States.
authors.forename: Britta
authors.initials: B
authors.lastname: Petersen
authors.affiliation: Immunology Research, Biogen, 115 Broadway, Cambridge, MA 02142, United States.
authors.forename: Luke
authors.initials: L
authors.lastname: Jandreski
authors.affiliation: Immunology Research, Biogen, 115 Broadway, Cambridge, MA 02142, United States.
authors.forename: Stefan
authors.initials: S
authors.lastname: Hamann
authors.affiliation: Immunology Research, Biogen, 115 Broadway, Cambridge, MA 02142, United States.
authors.forename: Taylor L
authors.initials: TL
authors.lastname: Reynolds
authors.affiliation: Immunology Research, Biogen, 115 Broadway, Cambridge, MA 02142, United States.
authors.forename: Timothy S
authors.initials: TS
authors.lastname: Zheng
authors.affiliation: Immunology Research, Biogen, 115 Broadway, Cambridge, MA 02142, United States. Electronic address: michael.mingueneau@biogen.com.
authors.forename: Michael
authors.initials: M
authors.lastname: Mingueneau
mesh_terms: D000818:Animals; D015551:Autoimmunity / Q000235:genetics / Q000276:immunology; D053264:B-Cell Activating Factor / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D005434:Flow Cytometry; D020869:Gene Expression Profiling / Q000379:methods; D018858:Germinal Center / Q000276:immunology / Q000378:metabolism; D007150:Immunohistochemistry; D007765:Lacrimal Apparatus / Q000276:immunology / Q000378:metabolism; D008297:Male; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D020411:Oligonucleotide Array Sequence Analysis; D012859:Sjogren's Syndrome / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D014985:Xerophthalmia / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014987:Xerostomia / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D053264:B-Cell Activating Factor; C505720:Tnfsf13b protein, mouse
keywords: Autoimmunity; B cells; BAFF; Ectopic germinal center; Sjögren's syndrome