Abstract: TH-OR123

B Cell Deficiency Inhibits Chronic Antibody Mediated Rejection in a Th1 and IL-10 Dependent Pathway in a Rat Kidney Transplant Model

Session Information

Category: Transplantation

  • 1701 Transplantation: Basic and Experimental

Authors

  • Panzer, Sarah E., University of Wisconsin Madison, Madison, Wisconsin, United States
  • Reese, Shannon, University of Wisconsin Madison, Madison, Wisconsin, United States
  • Wilson, Nancy A., University of Wisconsin Madison, Madison, Wisconsin, United States
  • Ptak, Lucille D, University of Wisconsin Madison, Madison, Wisconsin, United States
  • Renteria, Isabelle S, University of Wisconsin Madison, Madison, Wisconsin, United States
  • Djamali, Arjang, University of Wisconsin Madison, Madison, Wisconsin, United States
Background

The pathologic role of B cells in chronic antibody mediated rejection (cAMR) remains unclear.

Methods

We generated B cell deficient Lewis rats (B-/-) via CRISPR technology. Kidney transplantation was performed in 4 groups: syngeneic (Lewis to Lewis), allogeneic (Fisher to Lewis), sensitized (Fisher to Lewis 3 weeks following donor-specific blood transfusion), and allogeneic B cell deficient recipients (Fisher to B-/- Lewis). All animals were harvested at 6 months.

Results

cAMR was reduced in B-/- recipients compared to allogeneic and sensitized recipients based on Banff scores for microvascular inflammation (allogeneic: 3.0±1.7, sensitized: 4.6±0.5, B-/-: 1.5±0.6; P=0.001) and C4d staining (allogeneic: 1.5±0.6, sensitized: 2.2±0.8, B-/-: 0.5±0.6; P=0.05). Allograft deposition of IgM was significantly reduced in B-/- compared to allogeneic recipients (Fig1A). Intragraft macrophages and fibrosis by Picrosirius red stain demonstrated no differences among allogeneic, sensitized, and B-/- recipients (Fig1B). Th1 (IL-2 and IFN-gamma) and IL-10 cytokines by RT PCR were significantly reduced in B-/- compared to allogeneic recipients, but not Th2 (IL-4 and IL-6) or Th17 (Fig1C). Chronicity scores (Banff chronicity score = cg + ct + ci + cv) were elevated in allogeneic, sensitized, and B-/- recipients (3.0±1.7, 4.6±0.5, and 1.5±0.6, respectively).

Conclusion

B cell deficiency inhibits cAMR in a Th1 and IL-10 dependent pathway. Further studies are needed to determine the contributions from non-B cell mediated factors, such as innate immunity, to the development of fibrosis in chronic rejection.

Figure 1. B cell deficient recipients demonstrated reduced allograft inflammation. (A) Immunoflourescence showed absent antibody deposition in the allografts of B-/- recipients. (B) Fibrosis, as determined by Picorsirius red stain, was unchanged among allogeneic, sensitized, and B-/- recipients. (C) RT PCR of allografts demonstrated a reduction in Th1 cytokines (IL-2, IFN-gamma) and IL-10.

Funding

  • Other NIH Support