Purpose: The specific role of B cells in the pathogenesis of acute rejection remains unclear.

Methods: To address this question, we generated B cell deficient Lewis rats (B^-/-) via CRISPR technology with a targeted deletion of the Igh6 gene for IgM. Full mismatch kidney transplants were performed with Brown Norway (BN) donor to B^-/- recipients (N=7) and a control group of BN donors to wild type Lewis recipients (WT, N=6). All animals were given cyclosporine until harvest at 7 days.

Results: Cellular rejection was significantly reduced in B^-/- compared to WT based on Banff scores for tubulitis and interstitial inflammation (P=0.02 and 0.001, respectively, Figure 1A-B). The amount of graft infiltrating macrophages was reduced in B^-/- compared to WT (P=0.0001 by quantitative densitometry, Fig 1C-D). Measures of antibody mediated rejection showed reduced IgM DSA (P=0.03) and a trend towards reduced peritubular capillaritis (P=0.07) in B^-/- compared to WT. Serum BAFF levels were lower in B^-/- compared to WT (P=0.08). Flow cytometry confirmed absence of B cells in spleen, bone marrow, lymph node, and peripheral blood of the B^-/-. ELISPOT analysis demonstrated no antibody production in B^-/-. Assessment of splenic tissue in B^-/- demonstrated loss of architecture and frequent macrophages (Fig 2A). Typical germinal center formation was seen in WT (Fig 2B). Splenic T cells were seen in B^-/- and WT (Fig 2C and D, respectively). B^-/- lacked splenic B cells (Fig 2C), B cells were present in WT (Fig 2D).Conclusions: Our studies demonstrate B cell deficiency inhibits both antibody and T cell mediated rejection while also downregulating graft-infiltrating macrophages. The cellular mechanisms and alterations in lymphoid architecture that are involved in this cross-talk are under investigation.

CITATION INFORMATION: Panzer S, Reese S, Wilson Schlei N, Verhoven B, Xiang D, Zhong W, Djamali A. B Cell Deficiency Inhibits Both Antibody Mediated Rejection and T Cell Mediated Acute Rejection in a Rat Kidney Transplant Model. Am J Transplant. 2017;17 (suppl 3).

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