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Frontiers of Medicine

, Volume 11, Issue 4, pp 536–547 | Cite as

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

  • Jingjing Yan
  • Shuye Zhang
  • Jun Sun
  • Jianqing XuEmail author
  • Xiaoyang ZhangEmail author
Research Article

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.

Keywords

B cell HIV-1 phenotype functionality antiretroviral therapy 

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Notes

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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Copyright information

© Higher Education Press and Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  1. 1.Shanghai Public Health Clinical Center & Institutes of Biomedical SciencesFudan UniversityShanghaiChina

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