Abstract: TH-PO0438
Generation of IgG Autoantibodies Against Renal Self-Antigens in the Renal Lymph Nodes of a Murine Model of IgAN
Session Information
- Glomerular Diseases: Autoimmune Diseases
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology
Authors
- Nihei, Yoshihito, Department of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan
- Mori, Kazuaki, Department of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan
- Kadota, Nozomi, Department of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan
- Yamada, Koshi, Department of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan
- Suzuki, Hitoshi, Department of Nephrology, Juntendo University Urayasu Hospital, Chiba, Japan
- Suzuki, Yusuke, Department of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan
Group or Team Name
- Juntendo University
Background
We showed the involvement of IgA autoantibodies directed against mesangial cells in the pathogenesis of IgA nephropathy (IgAN) (Sci. Adv. 2023, Life Sci. Alliance. 2024, Kidney Int. Reports. 2025). In autoimmune diseases characterized by organ-specific autoantibodies, the draining lymph nodes of the target organ have been reported to contribute to disease pathogenesis. In the present study, we investigated the role of renal lymph nodes (RLNs) using a mouse model of IgAN.
Methods
GddY mice, a spontaneous model of IgAN, were used in this study, with BALB/c mice as controls. Single-cell RNA sequencing (scRNA-seq) and B cell receptor (BCR) repertoire analyses were performed on CD45+ cells isolated from the RLNs of 8-week-old BALB/c and gddY mice. The frequency of germinal center B cells (GCBs) in RLNs was evaluated by flow cytometry (FCM). Approximately 30 recombinant antibodies (rrAbs) were generated from BCR repertoire analysis data.
Results
scRNA-seq analysis identified 17 distinct cell clusters in RLNs. Among these, cluster 7 was uniquely observed in gddY mice. Differentially expressed gene analysis identified this cluster as GCBs (Figure). FCM revealed an increased frequency of IgG-expressing GCB cells in the RLNs of gddY mice. To determine whether GCBs formed in the RLNs targeted self-antigens, Western blot analysis was performed using proteins extracted from mouse kidneys. The results showed that clone rrAb#4 recognized proteins expressed in the kidney.
Conclusion
We identified the induction of IgG autoantibodies targeting renal self-antigen in the RLNs of gddY mice. Future studies will focus on identifying the target self-antigens and elucidating how these autoantibodies contribute to the pathogenesis of IgAN.
Cluster 7, corresponding to GCBs, was observed only in RLNs from gddY mice.
Funding
- Private Foundation Support