Regulatory B cells require antigen recognition for effective allograft tolerance induction

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Abstract

Through multiple mechanisms, regulatory B cells (Breg) have been shown to play an important role in the development of allograft tolerance. However, a careful understanding of the role of antigen-specificity in Breg-mediated allograft tolerance has remained elusive. In experimental models of islet and cardiac transplantation, it has been established that Bregs can be induced in vivo by anti-CD45RB ± anti-TIM1antibody treatment, resulting in prolonged, Breg-dependent allograft tolerance. The importance of Breg antigen recognition has been suggested but not confirmed through adoptive transfer experiments, using tolerant WT C57BL/6 animals challenged with either BALB/c or C3H grafts. However, the importance of receptor-specificity has not been formally tested. Here, we utilize the novel ovalbumin-specific B cell receptor transnuclear (OBI) mice in multiple primary tolerance and adoptive transfer experiments to establish that Breg-dependent allograft tolerance relies on antigen recognition by B cells. Additionally, we identify that this Breg-dependent tolerance relies on the function of transforming growth factor-β. Together, these experiments mark important progress toward understanding how best to improve Breg-mediated allograft tolerance.

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Kimura, S., Rickert, C. G., Kojima, L., Aburawi, M., Tanimine, N., Fontan, F., … Markmann, J. F. (2020). Regulatory B cells require antigen recognition for effective allograft tolerance induction. American Journal of Transplantation, 20(4), 977–987. https://doi.org/10.1111/ajt.15739

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