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

Transplantation. 2018 Mar;102(3):396-405. doi: 10.1097/TP.0000000000002010.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Allografts
  • Animals
  • B-Lymphocytes / physiology*
  • Inflammation / prevention & control*
  • Interferon-gamma / biosynthesis
  • Interleukin-10 / genetics
  • Kidney Transplantation*
  • Lymphocyte Activation
  • Macrophages / physiology*
  • Rats
  • Rats, Inbred BN
  • Rats, Inbred Lew
  • T-Lymphocytes / immunology


  • Interleukin-10
  • Interferon-gamma