Deficiency of B Cells but Not Mast Cells Ameliorates Chronic Allograft Damage in a Mouse Model for Renal Transplantation.
Michael Mengel, Konrad Famulski, Jessica Chan, Luis Hidalgo, Banu Sis, Philip Halloran. University of Alberta, Edmonton, Canada
Background: We recently observed that the number of B cells and mast cells increases with time post transplantation in human renal allografts. Furthermore these two cell types predominately accumulate in areas of interstitial fibrosis and tubular atrophy (IFTA), suggesting a potential pathogenetic role of these cell in the onset and/or progression of IFTA.
Design: We analyzed the long-term time course of transplanting a wild type allograft (CBA) into a B cell (B6.129S2-Igh-6-/-) or mast cell (C57BL/6-KitW-v/W-v) deficient recipient and compared the findings to respective controls (CBA into B6 wild type). This strain combination (CBA into B6) represents transplantation across complete MHC incompatibility. Transplants were done in a non-life supporting model without any treatment and thus developed the natural course of rejection. Transplanted kidneys were harvested on day 7, 14, 21, 42, and 60 (total n=150) and analyzed by histopathology according to Banff criteria.
Results: B cell deficient recipients: At early time points (day 7 and 14) no significant differences in terms of interstitial infiltrates were found between controls and deficient recipients. On day 7, B cell deficient recipients showed significantly more tubulitis (p=0.004), but on day 21 a trend towards less interstitial inflammation and tubulitis. From day 42 and persisting to day 60, B cell deficient recipients showed significantly less, only focally present interstitial infiltrates and tubulitis. This resulted in significantly less interstitial fibrosis on day 60.
Mast cell deficient recipients: On day 7 and day 14 the deficient recipients showed significantly more interstitial fibrosis compared to controls. More mast cell deficient mice showed extensive necrosis and arterial thrombosis at late time points of harvest, i.e. day 42 and day 60.
Conclusions: Absence of B cells in the recipient has no influence on early cellular rejection of mice renal allografts. In contrast long-term maintenance of the inflammatory response and thus onset of chronic injury is dependent on the presence of B cells. In contrast mast cell deficient recipients show more vigorous acute rejection, potentially indicating an immune-modulatory role for this cell type.
Category: Kidney (does not include tumors)
Wednesday, March 2, 2011 1:00 PM
Poster Session VI # 264, Wednesday Afternoon