Abstract: TH-PO0670
Dysregulation of the Th17 T-Follicular-Like Helper Cell: Naïve B Cell Interactions Enhance the Generation of IgA in IgAN
Session Information
- Glomerular Diseases: Immunopathogenesis and Targeted Therapeutics
November 06, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology
Authors
- Steers, Nicholas J., Columbia University, New York, New York, United States
- Sen, Leuna, Columbia University, New York, New York, United States
- Simpson, Jenna, Columbia University, New York, New York, United States
- Gharavi, Ali G., Columbia University, New York, New York, United States
Background
The dysregulated IgA1 response is a central defect in the development of IgA Nephropathy (IgAN). T-follicular cells (T-FH) have been shown to play an essential role in the generation of the humoral immune response in the germinal centers of lymph tissues. We have investigated the mechanism of the generation of IgA, focusing on the interactions of the T-FH like cell subpopulations with naïve B-cells to determine if there is an imbalance that favors the class-switching of naïve B-cells to IgA plasmablasts and memory B-cells.
Methods
Different subpopulations of T-FH like cells and B-cells were cell sorted from 15 Healthy Controls (HC), 16 IgAN, 11 Lupus Nephritis (LN), and 15 Polycystic Kidney Disease (PKD) patients, and co-cultured in the presence of a cognate antigen. IgA was measured from the supernatants from the co-culture experiments. Flow cytometry confirmed the presence of IgA+ B-cells.
Results
A significant increase in the IgA in the cell culture supernatants of autologous co-cultures of all T-FH like cells with naïve B-cells was observed in cells derived from IgAN patients compared to HC, LN, and PKD patients. To identify the subpopulation of T-FH like cells enhancing the generation and secretion of IgA, the T-FH like cells were sorted into Th17, Th2, and Th1 subpopulations and co-cultured with the autologous naïve B-cells. No IgA was detected in the autologous cocultures of the Th1 T-FH -like cells and naïve B-cells. Analysis of the Th2 T-FH like cells and naïve B-cells demonstrated no significant differences in the IgA detected in the cell culture supernatant between HC (6.5±2.4 ng/ml), IgAN (6.6±1.7 ng/ml), LN (6.7±1.9 ng/ml), and PKD (6.1±1.4 ng/ml) patients. However, significant differences were seen in the IgA supernatant concentrations of Th17 T-FH like cells and naïve B-cells derived from IgAN patients (25.4±7.4 ng/ml) compared to HC (16.8±2.6 ng/ml), LN (15.5±2.1 ng/ml), and PKD (15.3±2.9 ng/ml) patients. The Th2 and Th17 T-FH like cells and naïve B-cells interactions are being evaluated by single cell RNA sequencing.
Conclusion
Our data indicates a dysregulation in the Th17 T-FH like cell – naïve B-cell interactions in the enhanced generation of IgA in IgAN. Future studies will be directed towards identification of molecular programs leading to enhanced Th17 T-FH like cell activity in IgAN.
Funding
- NIDDK Support