Transplantation
Transplantation
5 years ago

Complete B Cell Deficiency Reduces Allograft Inflammation and Intragraft Macrophages in a Rat Kidney Transplant Model

Zhong, Weixiong, Rubinstein, C. Dustin, Xiang, Ding, Redfield, Robert R., Verhoven, Bret M., Panzer, Sarah E., Reese, Shannon R., Wilson, Nancy A.
Background Increasingly, it is being appreciated that B cells have broad roles beyond the humoral response and are able to contribute to and regulate inflammation. The specific role of B cells in the pathogenesis of early allograft inflammation remains unclear. Methods To address this question, we generated B cell–deficient (B−/−) Lewis rats via clustered regularly interspaced short palindromic repeats (CRISPR) technology. In a full mismatch transplant model, kidneys from Brown Norway donors were transplanted into B−/− Lewis recipients or wild type Lewis recipients. T cell–mediated rejection was attenuated with cyclosporine. Results Renal inflammation was reduced at 1 week after transplant (Banff scores for interstitial inflammation, microvascular inflammation, glomerulitis, and C4d) in allografts from B−/− recipients. The reduction in interstitial inflammation was predominantly due to a decline in graft infiltrating macrophages. Intragraft T-cell numbers remained unchanged. In addition, B-cell deficiency was associated with increased T regulatory cells and reduced splenic T follicular helper cells at baseline; and significantly increased intragraft and splenic IL-10 mRNA levels after transplant. In vitro, B−/− and wild type splenic T cells produced similar levels of IFN-γ in response to T cell–specific activation. Conclusions B-cell deficiency in this model produced an anti-inflammatory phenotype with a shift toward regulatory T-cell populations, production of anti-inflammatory cytokines (IL-10), and a reduction in allograft inflammation. These findings define a role for B cells to influence the cell populations and mediators involved in the pathogenesis of early allograft inflammation.

Publisher URL: https://journals.lww.com/transplantjournal/Fulltext/2018/03000/Complete_B_Cell_Deficiency_Reduces_Allograft.16.aspx

DOI: 10.1097/TP.0000000000002010

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