Graft-derived extracellular vesicles transported across subcapsular sinus macrophages elicit B cell alloimmunity after transplantation.
Graft-derived extracellular vesicles transported across subcapsular sinus macrophages elicit B cell alloimmunity after transplantation.
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DOI：
10.1126/scitranslmed.abb0122
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发表时间：
2021-03-17
影响因子：
17.1
通讯作者：
Morelli AE
中科院分区：
文献类型：
--
作者：
Zeng F;Chen Z;Chen R;Shufesky WJ;Bandyopadhyay M;Camirand G;Oberbarnscheidt MH;Sullivan MLG;Baty CJ;Yang MQ;Calderon M;Stolz DB;Erdos G;Pelanda R;Brennan TV;Catz SD;Watkins SC;Larregina AT;Morelli AE
尽管供体特异性抗体(DSA)在识别主要组织相容性复合体(MHC)抗原和介导移植排斥反应中发挥了作用，但淋巴组织中的受体B细胞如何以及在哪里遇到供体MHC抗原仍不清楚。与这个教条相反，我们在这里证明了供者白细胞从皮肤或心脏移植物中迁移出来对于小鼠的B或T细胞同种异体致敏并不是必需的。我们发现，小鼠皮肤和心脏移植物以及人皮肤移植物通过细胞外小泡(EV)释放无细胞供体MHC抗原，这些EV被淋巴结中的被膜下窦(SCS)巨噬细胞或脾中的类似巨噬细胞捕获。供体EV通过SCS巨噬细胞转运，EVS上的供体MHC分子被同种异体反应性B细胞识别。这触发了B细胞的激活和DSA的产生，而这两者都被SCS巨噬细胞耗尽所阻止。这些结果揭示了移植物衍生的EV和开放场所干扰EV的生物发生、运输或抑制同种异体反应性B细胞的启动或重新激活的功能的意想不到的作用。
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.
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影响因子：
2.7
作者：
Chong AS
通讯作者：
Chong AS
影响因子：
15.9
作者：
Hughes, Andrew D.;Zhao, Daqiang;Lakkis, Fadi G.
通讯作者：
Lakkis, Fadi G.
DOI：
10.1073/pnas.1513533112
发表时间：
2015-10-13
影响因子：
11.1
作者：
Harper, Simon J. F.;Ali, Jason M.;Pettigrew, Gavin J.
通讯作者：
Pettigrew, Gavin J.
DOI：
10.1073/pnas.092596999
发表时间：
2002-04-30
影响因子：
11.1
作者：
Chalasani, G;Dai, ZH;Lakkis, FG
通讯作者：
Lakkis, FG
影响因子：
4.4
作者：
Herrera, OB;Golshayan, D;Lechler, RI
通讯作者：
Lechler, RI