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.

中文翻译：

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调节性 B 细胞需要抗原识别才能有效诱导同种异体移植物耐受。

通过多种机制，调节性 B 细胞 (Breg) 已被证明在同种异体移植物耐受性的发展中发挥重要作用。然而，对抗原特异性在 Breg 介导的同种异体移植物耐受中的作用的仔细理解仍然难以捉摸。在胰岛和心脏移植的实验模型中，已经确定可以通过抗 CD45RB ± 抗 TIM1 抗体治疗在体内诱导 Bregs，从而导致长期的 Breg 依赖性同种异体移植物耐受。Breg 抗原识别的重要性已被提出但未通过过继转移实验得到证实，使用耐受性 WT C57BL/6 动物挑战 BALB/c 或 C3H 移植物。然而，受体特异性的重要性尚未经过正式测试。这里，我们在多个初级耐受和过继转移实验中利用新型卵清蛋白特异性 B 细胞受体跨核 (OBI) 小鼠来确定 Breg 依赖性同种异体移植耐受依赖于 B 细胞的抗原识别。此外，我们发现这种 Breg 依赖性耐受依赖于转化生长因子-β 的功能。总之，这些实验标志着在理解如何最好地提高 Breg 介导的同种异体移植物耐受性方面取得了重要进展。