Laboratory of Immunoregulation, NIAID, NIH, Bethesda, Maryland, USA.
J Virol. 2013 May;87(10):5800-11. doi: 10.1128/JVI.00094-13. Epub 2013 Mar 13.
Terminal differentiation of B cells and hypergammaglobulinemia are hallmarks of B-cell hyperactivity in HIV disease. Plasmablasts are terminally differentiating B cells that circulate transiently in the blood following infection or vaccination; however, in HIV infection, they arise early and are maintained at abnormally high levels in viremic individuals. Here we show that only a small fraction of plasmablasts in the blood of viremic individuals is HIV specific. Assessment of plasmablast immunoglobulin isotype distribution revealed increased IgG(+) plasmablasts in early and most prominently during chronic HIV viremia, contrasting with a predominantly IgA(+) plasmablast profile in HIV-negative individuals or in aviremic HIV-infected individuals on treatment. Of note, IgG is the predominant immunoglobulin isotype of plasmablasts that arise transiently in the blood following parenteral immunization. Serum immunoglobulin levels were also elevated in HIV-infected viremic individuals, especially IgG, and correlated with levels of IgG(+) plasmablasts. Several soluble factors associated with immune activation were also increased in the sera of HIV-infected individuals, especially in viremic individuals, and correlated with serum immunoglobulin levels, particularly IgG. Thus, our data suggest that while plasmablasts in the blood may contribute to the HIV-specific immune response, the majority of these cells are not HIV specific and arise early, likely from indirect immune-activating effects of HIV replication, and reflect over time the effects of chronic antigenic stimulation. Such B-cell dysregulation may help explain why the antibody response is inadequate in HIV-infected individuals, even during early infection.
B 细胞的终末分化和高丙种球蛋白血症是 HIV 病中 B 细胞过度活跃的标志。浆母细胞是终末分化的 B 细胞，在感染或接种疫苗后会短暂地在血液中循环；然而，在 HIV 感染中，它们很早就出现，并在病毒血症个体中保持异常高的水平。在这里，我们表明，病毒血症个体血液中的浆母细胞只有一小部分是 HIV 特异性的。评估浆母细胞免疫球蛋白同种型分布显示，在早期和慢性 HIV 病毒血症期间，IgG(+)浆母细胞增加，与 HIV 阴性个体或接受治疗的无病毒血症 HIV 感染者中主要为 IgA(+)浆母细胞的特征形成对比。值得注意的是，IgG 是在血液中短暂出现的浆母细胞的主要免疫球蛋白同种型。在 HIV 感染的病毒血症个体中，血清免疫球蛋白水平也升高，尤其是 IgG，并且与 IgG(+)浆母细胞水平相关。几种与免疫激活相关的可溶性因子也在 HIV 感染个体的血清中升高，尤其是在病毒血症个体中，并且与血清免疫球蛋白水平相关，特别是 IgG。因此，我们的数据表明，尽管血液中的浆母细胞可能有助于 HIV 特异性免疫反应，但这些细胞的大多数不是 HIV 特异性的，并且很早就出现，可能是由 HIV 复制的间接免疫激活作用引起的，并且随着时间的推移反映了慢性抗原刺激的影响。这种 B 细胞失调可能有助于解释为什么即使在早期感染时，HIV 感染个体的抗体反应也不足。
