T2 B Cells Are Expanded During Experimental Tolerance Protocol and Contribute to Skin Graft Survival

Abstract

We have recently reported that, in humans, tolerance to organ transplantation is associated with alterations in the transcription of B cell related genes and changes in the phenotypes of the circulating B cells, suggesting a “B cell signature” for transplant tolerance. Whether these B cells have a role in maintaining tolerance in humans is as yet unclear. Here we use an experimental mouse model of tolerance to investigate the contribution of B cells to the maintenance of tolerance. We demonstrate that B cells are required for long-term tolerance to MHC I mismatched skin grafts and that adoptive transfer of B cells, but not non-B cells, from tolerised mice can prolong skin allograft survival in naïve transplant recipients. Further, as in humans, tolerance is associated with an increase in Transitional-2 (T2) B cells, a subset previously reported to have regulatory capacity. T2 B cells from tolerised mice, but not from naïve animals, are capable of prolonging skin allograft survival following adoptive transfer to naïve recipients and suppressing T cell activation in vitro. The mechanisms involved in the regulatory function of T2 B cells will be discussed. These results suggest that the increase in T2 B cells in tolerance represents an increase in regulatory B cells that actively contribute to the maintenance of tolerance.