title: BAFF-driven autoimmunity requires CD19 expression.
abstract: B cell activating factor of the tumor necrosis factor family (BAFF or BLyS) is a critical factor for B cell survival and maturation. BAFF-transgenic (BAFF-Tg) mice develop autoimmunity that resembles systemic lupus erythematosus (SLE) in a T cell-independent but MyD88-dependent manner, implicating toll-like receptor (TLR) signaling. The specific B cell subtypes that make pro-inflammatory autoantibodies in BAFF-Tg mice are TLR-activated innate B cells known as marginal zone (MZ) and B1 B cells. These cells infiltrate the salivary glands and kidneys of diseased BAFF-Tg mice. However, loss of B1a or MZ B cells does not protect BAFF-Tg mice against disease, suggesting that B1b B cells might be the important pathogenic B cell subset. To test this hypothesis, we have generated BAFF-Tg mice that retained follicular B cells, but are deficient in B1a, B1b and MZ B cells, by crossing BAFF-Tg mice to CD19-deficient mice (BTg-CD19(-/-)). The BTg-CD19(-/-) mice did not produce autoantibodies and were protected from splenomegaly, kidney pathology and all signs of autoimmunity. This work suggests that B1b B cells, rather than MZ or B1a B cells, are sufficient and possibly required for the development of autoimmunity. Loss of the majority of innate-like B cells was able to protect BAFF-Tg mice from developing disease, so we can now conclude that autoimmunity induced by excessive BAFF production requires B1b B cells and CD19 signaling.
authors.affiliation: Faculty of Medicine, Nursing and Health Sciences, Department of Immunology, Central Clinical School, Monash University, Commercial Rd, Melbourne 3004, Australia; The Walter and Eliza Hall Institute of Medical Research, Molecular Medicine Division, 1G Royal Parade, Melbourne 3052, Australia; The Department of Experimental Medicine, University of Melbourne, Parkville, Victoria 3052, Australia.
authors.forename: Kirsten A
authors.initials: KA
authors.lastname: Fairfax
authors.affiliation: Faculty of Medicine, Nursing and Health Sciences, Department of Immunology, Central Clinical School, Monash University, Commercial Rd, Melbourne 3004, Australia.
authors.forename: Evelyn
authors.initials: E
authors.lastname: Tsantikos
authors.affiliation: Faculty of Medicine, Nursing and Health Sciences, Department of Immunology, Central Clinical School, Monash University, Commercial Rd, Melbourne 3004, Australia.
authors.forename: William A
authors.initials: WA
authors.lastname: Figgett
authors.affiliation: Faculty of Medicine, Nursing and Health Sciences, Department of Immunology, Central Clinical School, Monash University, Commercial Rd, Melbourne 3004, Australia.
authors.forename: Fabien B
authors.initials: FB
authors.lastname: Vincent
authors.affiliation: Faculty of Medicine, Nursing and Health Sciences, Department of Immunology, Central Clinical School, Monash University, Commercial Rd, Melbourne 3004, Australia.
authors.forename: Pin Shie
authors.initials: PS
authors.lastname: Quah
authors.affiliation: Faculty of Medicine, Nursing and Health Sciences, Department of Immunology, Central Clinical School, Monash University, Commercial Rd, Melbourne 3004, Australia.
authors.forename: Mélanie
authors.initials: M
authors.lastname: LePage
authors.affiliation: Faculty of Medicine, Nursing and Health Sciences, Department of Immunology, Central Clinical School, Monash University, Commercial Rd, Melbourne 3004, Australia.
authors.forename: Margaret L
authors.initials: ML
authors.lastname: Hibbs
authors.affiliation: Faculty of Medicine, Nursing and Health Sciences, Department of Immunology, Central Clinical School, Monash University, Commercial Rd, Melbourne 3004, Australia. Electronic address: Fabienne.Mackay@monash.edu.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Mackay
mesh_terms: D000818:Animals; D018941:Antigens, CD19 / Q000235:genetics*; D001323:Autoantibodies / Q000276:immunology; D015551:Autoimmunity / Q000235:genetics* / Q000276:immunology*; D053264:B-Cell Activating Factor / Q000378:metabolism*; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D003176:Complement C3 / Q000276:immunology; D005786:Gene Expression Regulation; D005921:Glomerulonephritis / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010641:Phenotype; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000378:metabolism
chemical_list: D018941:Antigens, CD19; D001323:Autoantibodies; D053264:B-Cell Activating Factor; D003176:Complement C3; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D051193:Toll-Like Receptors
keywords: Autoimmunity; B1b cells; BAFF; BAFF-transgenic; CD19; MZ B cells