Antibodies to Low-Copy Number RBC Alloantigen Convert a Tolerogenic Stimulus to an Immunogenic Stimulus in Mice.
Antibodies to Low-Copy Number RBC Alloantigen Convert a Tolerogenic Stimulus to an Immunogenic Stimulus in Mice.
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DOI：
10.3389/fimmu.2021.629608
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发表时间：
2021
影响因子：
7.3
通讯作者：
Hudson KE
中科院分区：
文献类型：
--
作者：
Jash A;Usaneerungrueng C;Howie HL;Qiu A;Luckey CJ;Zimring JC;Hudson KE
众所周知，表达同种抗原的红细胞能够在输血和妊娠中诱导强烈的体液同种抗体应答。然而，大多数输血受者和孕妇从未产生同种抗体，即使在重复暴露于外源RBC后也是如此。最近，红细胞已被用作细胞疗法-非常像输血，工程红细胞在某些情况下是高度免疫原性的，但不是其他人。在输血和基于RBC的治疗的动物模型中，不诱导免疫应答的RBC也引起耐受性。尽管有一个强大的现象学，但调节免疫与对RBC耐受性的机制仍然不清楚。然而，据报道，RBC上同种异体抗原的拷贝数是一个关键因素，非常低的拷贝数会导致无反应性（在人和小鼠中），也会导致小鼠耐受。最近，我们报道了对RBC抗原具有特异性的IgG 2c可以在输注表达该抗原的RBC后显著增强体液免疫应答。在此，我们报告了IgG 2c将具有低抗原拷贝数的RBC从致耐受性转化为免疫原性刺激。这些研究结果报告了第一个已知的刺激，诱导体液同种异体免疫低拷贝数RBC同种异体抗原，并确定了一个以前未描述的分子开关，有能力影响反应者与非反应者输血受体的表型。
Red blood cells expressing alloantigens are well known to be capable of inducing robust humoral alloantibody responses both in transfusion and pregnancy. However, the majority of transfusion recipients and pregnant women never make alloantibodies, even after repeat exposure to foreign RBCs. More recently, RBCs have been used as a cellular therapeutic—very much like transfusion, engineered RBCs are highly immunogenic in some cases but not others. In animal models of both transfusion and RBC based therapeutics, RBCs that do not induce an immune response also cause tolerance. Despite a robust phenomenology, the mechanisms of what regulates immunity vs. tolerance to RBCs remains unclear. However, it has been reported that copy number of alloantigens on the RBCs is a critical factor, with a very low copy number causing non-responsiveness (in both humans and mice) and also leading to tolerance in mice. Recently, we reported that an IgG2c specific for an RBC antigen can substantially enhance the humoral immune response upon transfusion of RBCs expressing that antigen. Herein, we report that an IgG2c converts RBCs with low antigen copy number from a tolerogenic to an immunogenic stimulus. These findings report the first known stimulus that induces humoral alloimmunization to a low copy number RBC alloantigen and identify a previously undescribed molecular switch that has the ability to affect responder vs. non-responder phenotypes of transfusion recipients.
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DOI：
10.1073/pnas.2002880117
发表时间：
2020-07-28
影响因子：
11.1
作者：
Ukidve, Anvay;Zhao, Zongmin;Mitragotri, Samir
通讯作者：
Mitragotri, Samir
影响因子：
2.9
作者：
Flegel, WA;Khull, SR;Wagner, FF
通讯作者：
Wagner, FF
影响因子：
7.5
作者：
Gruber, David R.;Richards, Amanda L.;Hudson, Krystalyn E.
通讯作者：
Hudson, Krystalyn E.
影响因子：
4.4
作者：
Arthur, Connie M.;Patel, Seema R.;Stowell, Sean R.
通讯作者：
Stowell, Sean R.
影响因子：
7.3
作者：
Shinde, Paurvi;Howie, Heather L.;Zimring, James C.
通讯作者：
Zimring, James C.