Passively transferred IgG enhances humoral immunity to a red blood cell alloantigen in mice
Passively transferred IgG enhances humoral immunity to a red blood cell alloantigen in mice
复制标题
DOI：
10.1182/bloodadvances.2019001299
复制
发表时间：
2020-04-14
期刊：
影响因子：
7.5
通讯作者：
Hudson, Krystalyn E.
中科院分区：
文献类型：
--
作者：
Gruber, David R.;Richards, Amanda L.;Hudson, Krystalyn E.
抗体通常被认为是作为适应性免疫应答的结果而发生的体液免疫的终点。然而，亲和力成熟的抗体可以在新的免疫应答开始时存在，最常见的是因为作为药物治疗的被动施用。目前的范例是免疫球蛋白M（IgM）、伊加和IgE增强随后的体液免疫。相比之下，IgG具有“双重作用”，即增强对可溶性抗原的反应，但抑制对红细胞（RBC）上抗原的反应（例如，使用抗RhD进行免疫预防）。在这里，我们报告了一个系统，其中被动抗体的RBC抗原促进了强大的细胞免疫反应，导致内源性CD 4（+）T细胞活化，生发中心的形成，抗体分泌和免疫记忆。该机制需要连接特定树突细胞亚群上的Fc γ受体，导致CD 4（-）T细胞活化和扩增。此外，抗体交叉增强对第三方抗原的反应，但只有当它在与抗体识别的抗原相同的RBC上表达时。重要的是，这些观察结果是IgG亚型特异性的。因此，这些研究结果表明，RBC同种异体抗原的抗体可以增强体液免疫的IgG亚型特异性的方式，并提供增强效果的机制阐明。
Antibodies are typically thought of as the endpoint of humoral immunity that occur as the result of an adaptive immune response. However, affinity-matured antibodies can be present at the initiation of a new immune response, most commonly because of passive administration as a medical therapy. The current paradigm is that immunoglobulin M (IgM), IgA, and IgE enhance subsequent humoral immunity. In contrast, IgG has a "dual effect" in which it enhances responses to soluble antigens but suppresses responses to antigens on red blood cells (RBCs) (eg, immunoprophylaxis with anti-RhD). Here, we report a system in which passive antibody to an RBC antigen promotes a robust cellular immune response leading to endogenous CD4(+) T-cell activation, germinal center formation, antibody secretion, and immunological memory. The mechanism requires ligation of Fc gamma receptors on a specific subset of dendritic cells that results in CD4(-) T-cell activation and expansion. Moreover, antibodies cross-enhance responses to a third-party antigen, but only if it is expressed on the same RBC as the antigen recognized by the antibody. Importantly, these observations were IgG subtype specific. Thus, these findings demonstrate that antibodies to RBC alloantigens can enhance humoral immunity in an IgG subtype-specific fashion and provide mechanistic elucidation of the enhancing effects.