Abstract: FR-PO861
B Cell Deficiency in a Rat Kidney Transplant Model Reduces Glomerular Basement Membrane Duplication in Early Transplant Glomerulopathy
Session Information
- Transplantation: Basic
October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Transplantation
- 1801 Transplantation: Basic
Authors
- Panzer, Sarah E., University of Wisconsin Madison, Madison, Wisconsin, United States
- Huang, Yabing, University of Wisconsin Madison, Madison, Wisconsin, United States
- Zhong, Weixiong, University of Wisconsin Madison, Madison, Wisconsin, United States
- Djamali, Arjang, University of Wisconsin Madison, Madison, Wisconsin, United States
Background
B cells play core roles in the humoral response and are able to contribute to cellular immunity, but the specific role of B cells in early transplant glomerulopathy (TG) remains unclear. We hypothesize B cell deficiency will attenuate the pathology of TG.
Methods
A rat kidney transplant model was used with 4 treatment groups: Syngeneic (Lewis to Lewis), Allogeneic (Fisher to Lewis), Sensitized (Fisher to Lewis 3 weeks following donor blood transfusion), or Allogeneic B cell deficient (B-/-) recipients (Fisher to B-/- Lewis). All animals were harvested at 3 or 6 months. The following 5 parameters were measured by electron microscopy: duplication of glomerular basement membrane (GBM), total length of GBM, diameter of endothelial cell (EC), height of EC, and layers of peritubular capillary basement membrane (PTCBM). The ratio of GBM injury and mean data was determined among these groups.
Results
At 3 months after transplant, GBM duplication was reduced between B-/- recipients and sensitized recipients (10.2±0.8% versus 6.5±0.7%; p=0.01). The percent of GBM with duplication was reduced at 6 months after transplant in B-/- recipients compared to allogeneic and sensitized recipients (B-/-:8.5±1.1%, allogeneic:17.2±0.8%, sensitized:32.6±3.3%; p<0.001) (Figure 1). The mean maximum diameter and the mean height of EC demonstrated no differences among allogeneic, sensitized, and B-/- recipients in both 3 and 6 months samples. PTCBM multilayering was also similar among allogeneic, sensitized, and B-/- recipients in both 3 and 6 months samples.
Conclusion
B cell deficiency in this model reduces the duplication of GBM in early TG. The GBM injury occurs before obvious EC injury and PTCBM multilayering. Future studies of B cell directed interventions are needed in TG.
Funding
- Other NIH Support