Introduction:

Regulatory B cells (Bregs) have shown several multiple mechanisms of suppression, including Treg induction and IL-10 production. Consistent with work of other groups on Breg function, we have identified that Breg-mediated tolerance is IL-10-dependent in our pancreatic islet transplant model. We have expanded this work to demonstrate that in vitro expanded Bregs (eBregs) require IL-10 for islet graft tolerance. Interestingly, here, we demonstrate that the eBreg-induced allograft tolerance varies in its dependence on IL-10 based on the type of the transplant.

Methods:

Initial allograft tolerance achieved through anti-CD45RB treatment. B cells were then isolated at day 100 and transferred to the [mu]MT mice. B cells were also isolated from naïve WT and IL-10-/- mice separately, co-cultured with irradiated CD40L expressing NIH-3T3 cells, BATF, IL-4, anti-TIM-1 and IL-21 for 8 days, then sorted for B cells. They were then injected into [mu]MT mice pre-cardiac transplant. Following this, we observed cardiac survival and analyzed blood and splenocytes for using flow cytometry. We assessed the ability of an in-vitro expanded Breg population to induce tolerance in the heart transplant model.

Results:

B cells from long-term-survival mice transferred to [mu]MT mice induce tolerance to heart transplant. We also identified that eBregs induce tolerance in a significant portion of the heart transplanted animals. Surprisingly, eBregs adoptively transferred from IL-10-/- mice are also capable of inducing tolerance at similar rates to eBregs from WT animals through the first month.

Conclusions:

eBregs are capable of producing tolerance in a significant portion of animals that receive a heart transplant. In contrast to the islet tolerance model, the prolonged survival of cardiac allograft is not dependent on IL-10. Thus, our data suggest that the specific mechanisms by which eBregs bring about tolerance is influenced by the type of allograft. These findings suggest that appreciating the role of the allograft tissue in tolerance development will be vital to optimizing the function of eBregs.

CITATION INFORMATION: Dai C., Lee K., Kojima L., Deng K., Kimura S., Rickert C., Yeh H., Markmann J. IL-10 Requirement in In Vitro Expanded Breg-Mediated Allograft Tolerance is Tissue Specific Am J Transplant. 2017;17 (suppl 3).

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