Abstract: SA-PO597
Characteristics of B Cells in IgA Nephropathy Model Mice
Session Information
- Glomerular Diseases: Immunology, Inflammation - II
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1202 Glomerular Diseases: Immunology and Inflammation
Authors
- Nihei, Yoshihito, Juntendo University Faculty of Medicine, Tokyo, Japan
- Fukao, Yusuke, Juntendo University Faculty of Medicine, Tokyo, Japan
- Suzuki, Hitoshi, Juntendo University Faculty of Medicine, Tokyo, Japan
- Suzuki, Yusuke, Juntendo University Faculty of Medicine, Tokyo, Japan
Background
The pathogenesis of IgA nephropathy (IgAN) is associated with dysregulation of immune system, however the characteristics of B cells that are responsible for production of nephritogenic IgA have been elusive. Recently, we have reported the abnormal B cells expressing APRIL are present in tonsils of human IgAN (JASN 28; 1227, 2017). Since abnormal antibody production seems to be the key feature in the pathogenesis of IgAN, we investigated characteristics of B cells in IgAN model mice, gddY mice, which we have established. Furthermore, we recently developed a novel culture system mimicking germinal center in mucosa, by which nearly 50 % of B cells undergo class switch (CS) to IgA. Therefore, the present study aimed to evaluate characteristics of B cells in gddY mice by using this novel culture system. First, we analyzed the proliferation of splenic B cells upon stimulation in vitro. Next, we examined their CS to IgA.
Methods
The proliferation of splenic B cells upon stimulation with membrane-bound IgM and CD40 were evaluated by Thymidine-uptake analysis. Naïve B cells from wild type mice and gddY mice were cultured for seven days by using newly developed culture system and the IgA CS was evaluated by flow cytometry.
Results
We found that B cells of gddY mice exhibited elevated proliferation rate than those of wild type mice in response to stimuli through CD40 and membrane-bound IgM. There was no significant difference in the frequency of CS to IgA between splenic B cells from gddY mice and those from wild mice.
Conclusion
These data indicate B cells in gddY mice may be hyper-sensitive to stimuli by antigen and T-cell help without increasing the frequency of IgA CS and suggest such a B-cell intrinsic factor may be involved in the pathology of IgAN.