title: BAFF Induces Tertiary Lymphoid Structures and Positions T Cells within the Glomeruli during Lupus Nephritis.
abstract: Tissue-specific immune responses play an important role in the pathology of autoimmune diseases. In systemic lupus erythematosus, deposits of IgG-immune complexes and the activation of complement in the kidney have long been thought to promote inflammation and lupus nephritis. However, the events that localize cells in non-lymphoid tertiary organs and sustain tissue-specific immune responses remain undefined. In this manuscript, we show that BAFF promotes events leading to lupus nephritis. Using an inducible model of systemic lupus erythematosus, we found that passive transfer of antinucleosome IgG into AID-/-MRL/lpr mice elevated autoantibody levels and promoted lupus nephritis by inducing BAFF production in the kidneys, and the formation of renal tertiary lymphoid structures (TLSs). Reducing BAFF in vivo prevented the formation of TLSs and lupus nephritis; however, it did not reduce immune cell infiltrates, or the deposits of IgG and complement in the kidney. Mechanistically, lowering BAFF levels also diminished the number of T cells positioned inside the glomeruli and reduced inflammation. Thus, BAFF plays a previously unappreciated role in lupus nephritis by inducing renal TLSs and regulating the position of T cells within the glomeruli.
authors.affiliation: Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
authors.forename: SunAh
authors.identifier: 0000-0002-6327-184X
authors.initials: S
authors.lastname: Kang
authors.affiliation: Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
authors.forename: Yuri
authors.initials: Y
authors.lastname: Fedoriw
authors.affiliation: Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
authors.forename: Ethan K
authors.initials: EK
authors.lastname: Brenneman
authors.affiliation: Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599; and.
authors.forename: Young K
authors.initials: YK
authors.lastname: Truong
authors.affiliation: Eli Lilly and Company, Indianapolis, IN 46285.
authors.forename: Kristine
authors.identifier: 0000-0002-3892-4191
authors.initials: K
authors.lastname: Kikly
authors.affiliation: Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599; barb_vilen@med.unc.edu.
authors.forename: Barbara J
authors.identifier: 0000-0003-0014-0022
authors.initials: BJ
authors.lastname: Vilen
mesh_terms: D000818:Animals; D053264:B-Cell Activating Factor / Q000276:immunology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D058501:Enzyme-Linked Immunospot Assay; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D007678:Kidney Glomerulus / Q000276:immunology*; D008181:Lupus Nephritis / Q000276:immunology*; D051379:Mice; D019463:Mice, Inbred MRL lpr; D000072717:Tertiary Lymphoid Structures / Q000276:immunology*
chemical_list: D053264:B-Cell Activating Factor; C505720:Tnfsf13b protein, mouse