Naïve B cells with low differentiation improve the immune reconstitution of HIV-infected patients

Jie Jia; Yu Zhao; Ji-Qun Yang; Dan-Feng Lu; Xiu-Ling Zhang; Jun-Hong Mao; Kun-Hua Wang; Jian-Hua Wang; Yi-Qun Kuang

doi:10.1016/j.isci.2022.105559

Naïve B cells with low differentiation improve the immune reconstitution of HIV-infected patients

iScience. 2022 Nov 13;25(12):105559. doi: 10.1016/j.isci.2022.105559. eCollection 2022 Dec 22.

Authors

Jie Jia^{1

2}, Yu Zhao^{1

2}, Ji-Qun Yang³, Dan-Feng Lu^{1

2}, Xiu-Ling Zhang³, Jun-Hong Mao^{1

2}, Kun-Hua Wang¹, Jian-Hua Wang⁴, Yi-Qun Kuang^{1

2}

Affiliations

¹ NHC Key Laboratory of Drug Addiction Medicine, First Affiliated Hospital of Kunming Medical University, Kunming Medical University, Kunming, Yunnan 650032, China.
² Scientific Research Laboratory Center, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, China.
³ Third People's Hospital of Kunming City/Drug Rehabilitation Hospital of Kunming City, Kunming, Yunnan 650041, China.
⁴ Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.

Abstract

Incomplete immune reconstitution happens in some HIV-infected patients who have achieved persistent viral suppression under antiretroviral therapy (ART). We performed single-cell RNA sequencing for peripheral blood mononuclear cells to analyze B cell receptor (BCR) repertoire and B cell subtypes in health controls (non-HIV-infected, HCs), HIV-infected immunological responders (IRs), and immunological nonresponders (INRs). We found that the dominant usage of IGHV gene segments of naïve B cells and memory B cells were IGHV3 and IGHV4, and the diversity of BCR repertoire was decreased in INRs. Differentiation trajectory analysis showed that the low differentiation of naïve B cells was related to satisfactory immune status. The cell cycle of B cells with immune-specific genes of IgD⁺ B cells was degraded in INRs, which was mediated by the anaphase-promoting complex/cyclosome pathway in the phase of G2/M checkpoints. These findings provide significant insights to understand the function of B cell-mediated immune response in immune reconstitution after HIV infection.

Keywords: Immune response; Immunology; Transcriptomics.