Transplant tolerance depends on regulatory T cells induced by TGF-β-producing regulatory B cells (P2168)

Abstract

Abstract Regulatory B cells (Bregs) have been shown to play a critical role in immune homeostasis and in autoimmunity models. We have recently demonstrated that combined anti-TIM-1 and anti-CD45RB antibody treatment results in tolerance to full MHC mismatch islet allografts in mice, generating Bregs that are necessary for tolerance, and capable of transferring tolerance to untreated animals. Herein, we demonstrate that adoptively transferred Bregs require the presence of Tregs to establish tolerance, and that adoptive transfer of Bregs increases the number of Tregs. Bregs induce significantly more Foxp3 expression in CD4+CD25- T cells, in vivo, compared to naive B cells. We also show that Bregs express the TGF-β associated latency-associated peptide (LAP). Furthermore, Breg-mediated graft prolongation post-adoptive transfer is abrogated by neutralization of TGF-β activity. Collectively, these findings suggest that in this model of antibody-induced transplantation tolerance, Bregs promote graft survival by promoting Treg development, possibly via TGF-β production.