Circulating Plasmablasts from Chronically Human Immunodeficiency Virus-Infected Individuals Predominantly Produce Polyreactive/Autoreactive Antibodies.
Circulating Plasmablasts from Chronically Human Immunodeficiency Virus-Infected Individuals Predominantly Produce Polyreactive/Autoreactive Antibodies.
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DOI：
10.3389/fimmu.2017.01691
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发表时间：
2017
影响因子：
7.3
通讯作者：
Zhang Z
中科院分区：
文献类型：
--
作者：
Liao H;Yu Y;Li S;Yue Y;Tao C;Su K;Zhang Z
了解慢性人类免疫缺陷病毒(HIV)感染过程中B细胞的反应对于激发广泛而有效的中和抗体(Abs)至关重要。在这项研究中，我们结合抗逆转录病毒疗法(ART)分析了慢性HIV感染者的浆母细胞谱系。在获得的72株重组单抗中，27.8%与HIV gp140弱结合，为非中和抗体。值得注意的是，56.9%是多反应，55.6%是自身反应。多反应/自身反应的显著特征并不局限于抗gp140抗体。此外，这些多反应/自身反应抗体在N-甲基-d-天冬氨酸受体(NMDAR)上与DWEYS表现出显著的交叉反应，这种结合诱导了SH-SY5Y细胞的凋亡。我们还发现，在慢性HIV感染者的浆母细胞库中，VH4-34利用和VH替换的频率更高，这可能有助于多聚/自身反应抗体的产生。综上所述，这些数据表明，接受抗逆转录病毒治疗的慢性HIV感染者的循环浆母细胞主要产生多聚/自身反应抗体，抗HIV中和能力最低，并可能与自身抗原发生交叉反应。这可能代表了慢性HIV感染过程中B细胞的另一种功能障碍。
Understanding the B-cell response during chronic human immunodeficiency virus (HIV) infection is essential for eliciting broad and potent neutralizing antibodies (Abs). In this study, we analyzed the plasmablast repertoire of chronically HIV-infected individuals in combination with antiretroviral therapy (ART). Among the obtained 72 recombinant monoclonal antibodies (mAbs), 27.8% weakly bound to HIV gp140 and were non-neutralizing. Remarkably, 56.9% were polyreactive and 55.6% were autoreactive. The prominent feature of being polyreactive/autoreactive is not limited to anti-gp140 Abs. Furthermore, these polyreactive/autoreactive Abs displayed striking cross-reactivity with DWEYS in the N-methyl-d-aspartate receptor (NMDAR), and this binding induced SH-SY5Y cell apoptosis. We also found higher frequencies of VH4-34 utilization and VH replacement in the plasmablast repertoire of chronically HIV-infected individuals, which may contribute to the generation of poly/autoreactive Abs. Taken together, these data demonstrate that circulating plasmablasts in chronically HIV-infected individuals experienced with ART predominantly produce poly/autoreactive Abs with minimal anti-HIV neutralizing capacity and potential cross-reactivity with autoantigens. This may represent another dysfunction of B cells during chronic HIV infection.