Regulatory B cells require antigen recognition for effective allograft tolerance induction
| Autor: | James F. Markmann, Kang Mi Lee, Naoki Tanimine, Kevin Deng, Charles G. Rickert, Lisa Kojima, Haley Tector, Mohamed M. Aburawi, Fermin Fontan, Heidi Yeh, Shoko Kimura |
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| Rok vydání: | 2020 |
| Předmět: |
Adoptive cell transfer
Regulatory B cells B-cell receptor 030230 surgery T-Lymphocytes Regulatory Article Mice 03 medical and health sciences 0302 clinical medicine In vivo Immune Tolerance Animals Immunology and Allergy Medicine Pharmacology (medical) B-Lymphocytes Regulatory Mice Inbred BALB C Mice Inbred C3H Transplantation geography geography.geographical_feature_category business.industry Allograft Tolerance Islet Mice Inbred C57BL Immunology Transplantation Tolerance business Function (biology) |
| Zdroj: | Am J Transplant |
| ISSN: | 1600-6135 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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