%A Jingjing Yan, Shuye Zhang, Jun Sun, Jianqing Xu, Xiaoyang Zhang %T Irreversible phenotypic perturbation and functional impairment of B cells during HIV-1 infection %0 Journal Article %D 2017 %J Front. Med. %J Frontiers of Medicine %@ 2095-0217 %R 10.1007/s11684-017-0592-x %P 536-547 %V 11 %N 4 %U {https://academic.hep.com.cn/fmd/EN/10.1007/s11684-017-0592-x %8 2017-12-04 %X

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 HA-specific 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.