Graft-derived extracellular vesicles transported across subcapsular sinus macrophages elicit B cell alloimmunity after transplantation
| Autor: | Mu-qing Yang, Catherine J. Baty, Adrian E. Morelli, Mara Sullivan, Sergio D. Catz, Michel Calderon, William J. Shufesky, Mohna Bandyopadhyay, Todd V. Brennan, Martin H. Oberbarnscheidt, Rao Chen, Furong Zeng, Zhizhao Chen, Geza Erdos, Adriana T. Larregina, Donna B. Stolz, Simon C. Watkins, Roberta Pelanda, Geoffrey Camirand |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Graft Rejection Allosensitization T cell Priming (immunology) Major histocompatibility complex Article 03 medical and health sciences Extracellular Vesicles Mice 0302 clinical medicine Antigen medicine Animals B cell B-Lymphocytes Mice Inbred BALB C biology integumentary system Chemistry Macrophages Alloimmunity General Medicine medicine.disease Cell biology Transplant rejection Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure biology.protein Heart Transplantation 030215 immunology |
| Zdroj: | Sci Transl Med |
| Popis: | Despite the role of donor-specific antibodies (DSAs) in recognizing major histocompatibility complex (MHC) antigens and mediating transplant rejection, how and where recipient B cells in lymphoid tissues encounter donor MHC antigens remains unclear. Contrary to the dogma, we demonstrated here that migration of donor leukocytes out of skin or heart allografts is not necessary for B or T cell allosensitization in mice. We found that mouse skin and cardiac allografts and human skin grafts release cell-free donor MHC antigens via extracellular vesicles (EVs) that are captured by subcapsular sinus (SCS) macrophages in lymph nodes or analog macrophages in the spleen. Donor EVs were transported across the SCS macrophages, and donor MHC molecules on the EVs were recognized by alloreactive B cells. This triggered B cell activation and DSA production, which were both prevented by SCS macrophage depletion. These results reveal an unexpected role for graft-derived EVs and open venues to interfere with EV biogenesis, trafficking, or function to restrain priming or reactivation of alloreactive B cells. |
| Databáze: | OpenAIRE |
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