Irreversible phenotypic perturbation and functional impairment of B cells during HIV-1 infection
- Author:
Yan JINGJING
1
;
Zhang SHUYE
;
Sun JUN
;
Xu JIANQING
;
Zhang XIAOYANG
Author Information
1. Shanghai Public Health Clinical Center & Institutes of Biomedical Sciences
- Keywords:
B cell;
HIV-1;
phenotype;
functionality;
antiretroviral therapy
- From:
Frontiers of Medicine
2017;11(4):536-547
- CountryChina
- Language:Chinese
-
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 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.
