@ARTICLE{10.3389/fimmu.2017.01691, AUTHOR={Liao, Hongyan and Yu, Yangsheng and Li, Song and Yue, Yinshi and Tao, Chuanmin and Su, Kaihong and Zhang, Zhixin}, TITLE={Circulating Plasmablasts from Chronically Human Immunodeficiency Virus-Infected Individuals Predominantly Produce Polyreactive/Autoreactive Antibodies}, JOURNAL={Frontiers in Immunology}, VOLUME={8}, YEAR={2017}, URL={https://www.frontiersin.org/articles/10.3389/fimmu.2017.01691}, DOI={10.3389/fimmu.2017.01691}, ISSN={1664-3224}, ABSTRACT={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.} }