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Irreversible phenotypic perturbation and functional impairment of B cells during HIV-1 infection

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An Erratum to this article was published on 11 June 2019

This article has been updated

Abstract

Human immunodeficiency virus type 1 (HIV-1) infection can damage humoral immunity. The knowledge of B cell perturbations during chronic HIV-1 infection and their recovery after combined antiretroviral therapy (cART) is not complete yet, and thus attempts to further improve humoral immunity are impeded. In this study, an HIV-1 chronically infected cohort with similar demographics, infection history, genetic background, and HIV-1 genotype was established to probe B cell perturbations. Results showed that the B cells from this cohort were highly activated and prone to cell death, and B cell compartments were altered significantly. Notably, although cART partially reversed the hyperactivation and reduced tissue-like memory B cells, other B cell perturbations, including impaired expression of survival factor Bcl-2, costimulatory molecules, and shrunken resting memory B cells, were irreversible. Further functional characterization revealed that the influenza HAspecific antibody-secreting cells were significantly lower during HIV-1 infection, whereas the recalled antibody response to HIV-1-specific antigens was decreased after cART. Finally, CpG plus R848 treatment increased the survival of B cells and memory B cells in vitro from HIV-1-infected patients. In conclusion, this study identified irreversible B cell immune perturbations in chronic HIV-1 infections regardless of cART and proposed the potential strategy to enhance B cell functions through the improvement of cell survival.

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Change history

  • 20 January 2018

    The original version of this article unfortunately contained a mistake. One of the authors of this article has been misspelled. Xiaoyang Zhang should be Xiaoyan Zhang. The update is also provided here.

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Acknowledgements

This work was supported by the 973 Program (No. 2014CB542502), National Natural Science Foundation of China (No. 81561128008), Chinese National Grand Program on Key Infectious Disease Control and Prevention (No. 2017ZX10202102), and Shanghai ShenKang Hospital Development Center (No. SHDC12014104).

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  1. Jingjing Yan and Shuye Zhang contributed equally to this study.

Authors and Affiliations

  1. Shanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Fudan University, Shanghai, 201508, China

    Jingjing Yan, Shuye Zhang, Jun Sun, Jianqing Xu & Xiaoyang Zhang

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  1. Jingjing Yan
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  2. Shuye Zhang
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  3. Jun Sun
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  4. Jianqing Xu
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Correspondence to Jianqing Xu or Xiaoyang Zhang.

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Yan, J., Zhang, S., Sun, J. et al. Irreversible phenotypic perturbation and functional impairment of B cells during HIV-1 infection. Front. Med. 11, 536–547 (2017). https://doi.org/10.1007/s11684-017-0592-x

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