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Regulatory B cells require antigen recognition for effective allograft tolerance induction
Author(s) -
Kimura Shoko,
Rickert Charles G.,
Kojima Lisa,
Aburawi Mohamed,
Tanimine Naoki,
Fontan Fermin,
Deng Kevin,
Tector Haley,
Mi Lee Kang,
Yeh Heidi,
Markmann James F.
Publication year - 2020
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/ajt.15739
Subject(s) - regulatory b cells , adoptive cell transfer , medicine , immunology , transplantation , immune tolerance , antigen , immune system , t cell , interleukin 10
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.