In mice liver transplantation, the liver allografts can be accepted across fully mismatched MHC without immunosuppression. After transplantation, T cells infiltrate into the graft in the early post-transplant phase, but they are markedly reduced in the long term survival grafts due to apoptosis. Interestingly, the long-term survival liver allograft contains lymphocyte aggregations including B cells. In the past few years, some studies have provided evidence that B cells have an important role in transplant tolerance, and some subsets of B cells are inherently tolerogenic. To understand the role of B cells in liver transplantation tolerance, in this study, we characterized the phenotype and examined the function of the B cells in mouse liver allografts using both immunohistochemistry and flow cytometry approaches. For donors, B7H1^-/- and IFNγR1^-/- mice were used for the rejection model; B6 mice were for the tolerance model and C3H/He and B10.BR mice were used as recipients. There were very few B cells in the rejected grafts, but markedly more B cells had accumulated in tolerant grafts. In the long surviving grafts, the lymphocyte aggregation contains B220⁺,CD4⁺, and CD11b⁺ cells. There was no evidence that the aggregates contained endothelial venule-like vessels, suggesting no tertiary lymphoid tissues were formed. Almost all of the B cells expressed activation markers (CD44, CD69, MHC class II). The majority population of the B cells in spleen is follicular B cells (CD21^LoCD23⁺CD93^–), which is comparable with CD21^LoCD23^–CD93^– in the liver allograft. This population's function is not well known. B1a cells (CD5⁺CD43⁺) were identified at an early phase, but there were very few in the long-term surviving grafts. There are few germinal center B cells (GL-7⁺), plasma cells (CD138⁺), in before and after transplantation. The B cells were isolated from the liver allograft or spleen from the long surviving recipients and used for the function test. The B cells from the liver allograft were more suppressive for alloactivated T cells than the B cells from the spleen. In conclusion, B cells aggregated in liver allografts may play an important role in induction and/or maintenance of liver transplant tolerance.

CITATION INFORMATION: Morita M, Asonye G, Gupta N, Fung J, Miller C, Qian S, Lu L. B Cells in Liver Transplant Tolerance. Am J Transplant. 2017;17 (suppl 3).

« Back to 2017 American Transplant Congress