Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
J Exp Med. 2011 Oct 24;208(11):2237-49. doi: 10.1084/jem.20110363. Epub 2011 Oct 10.
The initial antibody response to HIV-1 is targeted to envelope (Env) gp41, and is nonneutralizing and ineffective in controlling viremia. To understand the origins and characteristics of gp41-binding antibodies produced shortly after HIV-1 transmission, we isolated and studied gp41-reactive plasma cells from subjects acutely infected with HIV-1. The frequencies of somatic mutations were relatively high in these gp41-reactive antibodies. Reverted unmutated ancestors of gp41-reactive antibodies derived from subjects acutely infected with HIV-1 frequently did not react with autologous HIV-1 Env; however, these antibodies were polyreactive and frequently bound to host or bacterial antigens. In one large clonal lineage of gp41-reactive antibodies, reactivity to HIV-1 Env was acquired only after somatic mutations. Polyreactive gp41-binding antibodies were also isolated from uninfected individuals. These data suggest that the majority of gp41-binding antibodies produced after acute HIV-1 infection are cross-reactive responses generated by stimulating memory B cells that have previously been activated by non-HIV-1 antigens.
人体对 HIV-1 的初始抗体反应针对的是包膜 (Env) gp41，这种非中和性抗体对于控制病毒血症无效。为了了解 HIV-1 传播后不久产生的 gp41 结合抗体的起源和特征，我们从急性感染 HIV-1 的受试者中分离和研究了 gp41 反应性浆细胞。这些 gp41 反应性抗体的体细胞突变频率相对较高。源自急性感染 HIV-1 的受试者的 gp41 反应性抗体的回复未突变的祖先通常与自体 HIV-1 Env 不反应；然而，这些抗体具有多反应性，并且经常与宿主或细菌抗原结合。在一个大型的 gp41 反应性抗体克隆谱系中，只有在体细胞突变后，才能获得对 HIV-1 Env 的反应性。也从未感染的个体中分离出了具有多反应性的 gp41 结合抗体。这些数据表明，急性 HIV-1 感染后产生的大多数 gp41 结合抗体是由以前被非 HIV-1 抗原激活的记忆 B 细胞刺激产生的交叉反应性应答。
