title: Association of BAFF/BLyS overexpression and altered B cell differentiation with Sjögren's syndrome.
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.
authors.affiliation: The Garvan Institute of Medical Research, Department of Arthritis and Inflammation, Darlinghurst, NSW, Australia.
authors.forename: Joanna
authors.initials: J
authors.lastname: Groom
authors.forename: Susan L
authors.initials: SL
authors.lastname: Kalled
authors.forename: Anne H
authors.initials: AH
authors.lastname: Cutler
authors.forename: Carl
authors.initials: C
authors.lastname: Olson
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Woodcock
authors.forename: Pascal
authors.initials: P
authors.lastname: Schneider
authors.forename: Jurg
authors.initials: J
authors.lastname: Tschopp
authors.forename: Teresa G
authors.initials: TG
authors.lastname: Cachero
authors.forename: Marcel
authors.initials: M
authors.lastname: Batten
authors.forename: Julie
authors.initials: J
authors.lastname: Wheway
authors.forename: Davide
authors.initials: D
authors.lastname: Mauri
authors.forename: Dana
authors.initials: D
authors.lastname: Cavill
authors.forename: Tom P
authors.initials: TP
authors.lastname: Gordon
authors.forename: Charles R
authors.initials: CR
authors.lastname: Mackay
authors.forename: Fabienne
authors.initials: F
authors.lastname: Mackay
mesh_terms: D000367:Age Factors; D000818:Animals; D015551:Autoimmunity; D053264:B-Cell Activating Factor; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D015870:Gene Expression; D006801:Humans; D007108:Immune Tolerance; D008565:Membrane Proteins / Q000097:blood / Q000235:genetics* / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012463:Saliva / Q000378:metabolism; D012859:Sjogren's Syndrome / Q000209:etiology / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D013045:Species Specificity; D013363:Submandibular Gland / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000276:immunology*
chemical_list: D053264:B-Cell Activating Factor; D008565:Membrane Proteins; C505719:TNFSF13B protein, human; C505720:Tnfsf13b protein, mouse; D014409:Tumor Necrosis Factor-alpha