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Abstract: PO1809

Dysregulation of B-Cell Differentiation in IgA Nephropathy Model Mice

Session Information

Category: Glomerular Diseases

  • 1202 Glomerular Diseases: Immunology and Inflammation

Authors

  • Nihei, Yoshihito, Department of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan
  • Suzuki, Hitoshi, Department of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan
  • Fukao, Yusuke, Department of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan
  • Nakayama, Maiko, Department of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan
  • Lee, Mingfeng, Department of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan
  • Kato, Rina, Department of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan
  • Kano, Toshiki, Department of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan
  • Makita, Yuko, Department of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan
  • Suzuki, Yusuke, Department of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan
Background

Several novel drugs targeting B cells are reported to be effective in the treatment of IgA nephropathy (IgAN). On the other hand, we have reported that the abnormal B cells expressing APRIL (A proliferation-inducing ligand) are present in tonsils of human IgAN. Given these reports, dysregulation of B cells may be involved in the pathogenesis of IgAN. To elucidate the abnormality in B cells of IgAN, we analyzed characteristics of B cells by using IgAN prone mice with (O-ddY) or without (NO-ddY) full onset of this disease. 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. Here, we aim to evaluate characteristics of B cells in O-ddY mice using this novel B cell culture system.

Methods

Splenic B cells from O-ddY or NO-ddY mice were stimulated with membrane-bound IgM and CD40 for 48h and then proliferation of B cells was evaluated by Thymidine-uptake analysis. To examine CS to IgA, naïve splenic B cells from O-ddY or NO-ddY mice were cultured for seven days under the newly developed culture system. The frequency of IgA CS was evaluated by flow cytometry.

Results

We found that naïve B cells of O-ddY proliferated more than those of NO-ddY mice in response to stimuli through CD40 and membrane-bound IgM. There was no significant difference in the frequency of class switch to IgA between splenic B cells from O-ddY mice and those from NO-ddY mice.

Conclusion

These data indicate that B cells in O-ddY mice are hyper-sensitive to stimuli by antigen and T-cell help without increasing the frequency of IgA class switch and suggest that such dysregulation of B cells may be involved in the pathogenesis of IgAN