Scarcely one would argue that donor-specific B cells and antibodies contribute to rejection of transplants. However, studies published in the past few years have provided evidence that B cells have important role in transplant tolerance, and some subsets of B cells are inherently tolerogenic. The underlying mechanisms remain unclear. In this study, we investigated T, B and myeloid cells in rejecting (IFN-gR^-/-) and tolerant (WT) mouse liver allografts using both immunohistchemstry and flow cytometry approaches. There were very few B cells in rejecting grafts, but markedly more B cells were accumulated in tolerant grafts which initiated in 1-2 week, gradually formed lymphoid aggregates, mainly distributed under liver capsule and some inside of lobules. At early phase post transplant, the tolerant liver grafts were mainly infiltrated with T cells (~CD8 50-60%, CD4 20%, CD11b 2-5%, CD19 1%), while in long-term survived grafts, they mainly contained B and myeloid cells (~CD8 10%, CD4 20%, CD11b 30%, CD19 30%). T and myeloid cells were located in inside of aggregates and surrounded by B cells, suggesting their intimate interactions. 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), and consisted of marginal zone B cells (CD21⁺CD23^–CD93^–), follicular B cells (CD21^–CD23⁺CD93^–), germinal center B cells (GL-7⁺), plasma cells (CD138⁺), B1 cells (CD21^–CD23^–CD93^–) and Breg cells (CD5⁺CD1d⁺). B1a cells (CD5⁺) were identified at early phase, but very few in long-termed survived grafts, while very few follicular B cells at early phase, but clearly identified in long survived grafts, suggesting their distinguished roles in induction of liver transplant tolerance.

CITATION INFORMATION: Morita M, Enyindah-Asonye G, Gupta N, Fung J, Qian S, Lu L. The Role of B Cells in Liver Transplant Tolerance. Am J Transplant. 2016;16 (suppl 3).

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