BAFF induces tertiary lymphoid structures and positions T cells within the Glomeruli during lupus nephritis

Sun Ah Kang, Yuri Fedoriw, Ethan K. Brenneman, Young K. Truong, Kristine Kikly, Barbara J. Vilen

Research output: Research - peer-reviewArticle

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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.

LanguageEnglish (US)
Pages2602-2611
Number of pages10
JournalJournal of Immunology
Volume198
Issue number7
DOIs
StatePublished - Apr 1 2017

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Lupus Nephritis
T-Lymphocytes
Kidney
Tertiary Lymphoid Structures
Immunoglobulin G
Systemic Lupus Erythematosus
Inflammation
Inbred MRL lpr Mouse
Complement Activation
Antigen-Antibody Complex
Autoantibodies
Autoimmune Diseases
Pathology

ASJC Scopus subject areas

  • Immunology

Cite this

BAFF induces tertiary lymphoid structures and positions T cells within the Glomeruli during lupus nephritis. / Kang, Sun Ah; Fedoriw, Yuri; Brenneman, Ethan K.; Truong, Young K.; Kikly, Kristine; Vilen, Barbara J.

In: Journal of Immunology, Vol. 198, No. 7, 01.04.2017, p. 2602-2611.

Research output: Research - peer-reviewArticle

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AU - Vilen,Barbara J.

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