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.
This work was supported by National Institute of Allergy and Infectious Diseases/National Institutes of Health Grants R01AI070984, R21AI105613, and R21AR064951 (to B.J.V.) and the Alliance for Lupus Research (to B.J.V.). The Flow Cytometry Core, Microscopy Services Core Laboratory, Histology Core Laboratory, and the Lineberger Cancer Center Biostatisitics Core Facility (all at the University of North Carolina at Chapel Hill) were supported by National Cancer Institute/National Institutes of Health Core Grant P30CA016086.
The online version of this article contains supplemental material.
Abbreviations used in this article:
- dendritic cell
- follicular dendritic cell
- IgG immune complex
- systemic lupus erythematosus
- follicular helper T cell
- tertiary lymphoid structure.
- Received February 16, 2016.
- Accepted January 26, 2017.
- Copyright © 2017 by The American Association of Immunologists, Inc.