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

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.

SUBMITTER: Jia J

PROVIDER: S-EPMC9708917 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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

Jia Jie J Zhao Yu Y Yang Ji-Qun JQ Lu Dan-Feng DF Zhang Xiu-Ling XL Mao Jun-Hong JH Wang Kun-Hua KH Wang Jian-Hua JH Kuang Yi-Qun YQ

iScience 20221113 12

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 <i>IGHV</i> gene segments of naïve B c ...[more]

PMID: 36465118

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Project description:Little is known regarding the restoration of the specific immune response after combined antiretroviral therapy (cART) and anti-tuberculosis (TB) therapy introduction among TB-HIV patients. In this study, we examined the immune response of TB-HIV patients to Mycobacterium tuberculosis (Mtb) antigens to evaluate the response dynamics to different antigens over time. Moreover, we also evaluated the influence of two different doses of efavirenz and the factors associated with immune reconstitution.This is a longitudinal study nested in a clinical trial, where cART was initiated during the baseline visit (D0), which occurred 30 ± 10 days after the introduction of anti-TB therapy. Follow-up visits were performed at 30, 60, 90 and 180 days after cART initiation. The production of IFN-? upon in vitro stimulation with Mtb antigens purified protein derivative (PPD), ESAT-6 and 38 kDa/CFP-10 using ELISpot was examined at baseline and follow-up visits.Sixty-one patients, all ART-naïve, were selected and included in the immune reconstitution analysis; seven (11.5%) developed Immune Reconstitution Inflammatory Syndrome (IRIS). The Mtb specific immune response was higher for the PPD antigen followed by 38 kDa/CFP-10 and increased in the first 60 days after cART initiation. In multivariate analysis, the variables independently associated with increased IFN-? production in response to PPD antigen were CD4+ T cell counts <200 cells/mm3 at baseline, age, site of tuberculosis, 800 mg efavirenz dose and follow-up CD4+ T cell counts. Moreover, the factors associated with the production of IFN-? in response to 38 kDa/CFP-10 were detectable HIV viral load (VL) and CD4+ T cell counts at follow-up visits of ?200 cells/mm3.These findings highlight the differences in immune response according to the specificity of the Mtb antigen, which contributes to a better understanding of TB-HIV immunopathogenesis. IFN-? production elicited by PPD and 38 kDa/CFP-10 antigens have a greater magnitude compared to ESAT-6 and are associated with different factors. The low response to ESAT-6, even during immune restoration, suggests that this antigen is not adequate to assess the immune response of immunosuppressed TB-HIV patients.

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

Publications

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

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