Molecular characterization of the cervical and systemic B-cell repertoire

Gaudet, Ryan G.; Breden, Felix; Plummer, Frank; Berry, Jody D.

doi:10.4161/mabs.3.2.14858

Cited by 6 publications

(4 citation statements)

References 74 publications

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“…Until now, few studies have assessed the nature of B-cells involved in production of Abs in the context of natural immunity against HIV. The detailed characterization of the Ig repertoire of cervical and systemic B-cells from a Kenyan HESN individual revealed that site-specific responses occur with unique regulation of tolerance and recruitment into local memory or blast B-cell compartments, and the infusion of systemic post-germinal center (GC) B-cells to the cervix seems to be a common event [ 76 ]. Further understanding the nature and how B-cell populations are solicited to fight against HIV appears important to the design of preventive approaches.…”

Section: Innate B-cells and Blys/baff In Natural Immunity To Hivmentioning

confidence: 99%

Natural Immunity to HIV: A Template for Vaccine Strategies

Fourcade

Poudrier

Roger

2018

Viruses

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Africa accounts for the majority of global human immunodeficiency virus (HIV) infections, most of which affect women through heterosexual intercourse. Currently, there is no cure for HIV and the development of vaccines and microbicides remains the best solution to eradicate the pandemic. We and others have identified HIV highly-exposed seronegative (HESN) individuals among African female commercial sex workers (CSWs). Analyses of genital samples from HESNs have demonstrated potent innate and anti-inflammatory conditions, HIV-specific CD4+ and CD8+ T-cells as well as immunoglobulins (Igs), and increased regulatory cell populations, all of which support a delicate balance between strength and control against HIV intrusion. Moreover, we have recently shown that frequencies of innate marginal zone (MZ) B-cells are decreased in the blood of HESNs when compared to HIV-uninfected non-CSW women, suggesting their recruitment to peripheral sites. This coincides with the fact that levels of B lymphocyte stimulator (BLyS/BAFF), known to shape the MZ pool and whose overexpression leads to MZ deregulation in HIV-infected progressors, are significantly lower in the blood of HESNs when compared to both HIV-infected CSWs and HIV-uninfected non-CSW women. Interestingly, MZ B-cells can bind HIV gp120 and produce specific IgG and IgA, and have a propensity for B regulatory potential, which could help both the fight against HIV and maintenance of low inflammatory conditions in HESNs. HESN individuals provide an exceptional opportunity to identify important clues for the development of protective devices, and efforts should aim at soliciting immune responses observed in the context of their natural immunity to HIV.

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Section: Innate B-cells and Blys/baff In Natural Immunity To Hivmentioning

confidence: 99%

Natural Immunity to HIV: A Template for Vaccine Strategies

Fourcade

Poudrier

Roger

2018

Viruses

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“…Until now, few studies have assessed B-cell expression profiles in the context of natural immunity against HIV. The detailed characterization of the Ig repertoire of cervical and systemic B-cells from a Kenyan HESN individual revealed that site-specific responses occur with unique regulation of tolerance and recruitment into local memory or blast B-cell compartments, and the infusion of systemic post-germinal center (GC) B-cells to the cervix seems to be a common event 14 . Understanding the nature and how these B-cell populations are solicited appears important to the design of preventive approaches.…”

mentioning

confidence: 99%

Blood B Lymphocyte Stimulator (BLyS)/BAFF levels may reflect natural immunity to HIV in highly exposed uninfected Beninese Commercial Sex Workers

Sabourin-Poirier

Fourcade

Chagnon-Choquet

et al. 2016

Sci Rep

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We have previously shown that excess B lymphocyte Stimulator (BLyS)/BAFF in plasma and on surface of blood dendritic cells (DC) of HIV-infected progressors coincides with B-cell dysregulations and increased frequencies of “precursor” innate marginal zone (MZ)-like B-cells. In contrast, both blood BLyS levels and frequencies of this population remained unaltered in HIV elite-controllers. Based on these observations, we hypothesized that control of BLyS and innate B-cell status could be associated with natural immunity against HIV infection. Therefore, we assessed blood BLyS levels and B-cell status in HIV highly-exposed commercial sex workers (CSWs) from Benin. We found blood BLyS levels of HIV-uninfected CSWs were lower than those observed in both HIV-infected CSW and HIV-uninfected non-CSW groups. Furthermore, levels of BLyS expression on blood T-cells and monocytes were lower in HIV-uninfected CSWs when compared to HIV-infected CSWs, but higher than those observed for HIV-uninfected non-CSWs. Concomitantly, HIV-infected CSWs presented a dysregulated blood B-cell compartment, characterized by increased total IgG1, increased frequencies of populations presenting immature and/or innate profiles and a higher ratio of IgG+/IgA+ plasmablasts. In contrast, relatively low levels of BLyS in the blood of HIV-uninfected CSWs coincided with a rather preserved B-cell compartment.

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“… 57 , 58 The isotypes of memory B cells can vary between individuals, and the locally present spectrum of B cells overlaps with, but is distinct from, systemic B-cells. 59 This makes it particularly intriguing to investigate local immune responses, detectable in first-void urine. Furthermore, our study highlights the limited neutralizing capacity of these naturally induced antibodies, aligning with existing literature.…”

Section: Discussionmentioning

confidence: 99%

HPV-specific antibodies in female genital tract secretions captured via first-void urine retain their neutralizing capacity

Téblick,

Lipovac,

Molenberghs

et al. 2024

Human Vaccines & Immunotherapeutics

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Human papillomavirus (HPV) vaccines, primarily relying on neutralizing antibodies, have proven highly effective. Recently, HPV-specific antibodies have been detected in the female genital tract secretions captured by first-void urine (FVU), offering a minimally invasive diagnostic approach. In this study, we investigated whether HPV16-specific antibodies present in FVU samples retain their neutralizing capacity by using pseudovirion-based neutralization assays. Paired FVU and serum samples (vaccinated n = 25, unvaccinated n = 25, aged 18–25) were analyzed using two orthogonal pseudovirion-based neutralization assays, one using fluorescence microscopy and the other using luminescence-based spectrophotometry. Results were compared with HPV16-specific IgG concentrations and correlations between neutralizing antibodies in FVU and serum were explored. The study demonstrated the presence of neutralizing antibodies in FVU using both pseudovirion-based neutralization assays, with the luminescence-based assay showing higher sensitivity for FVU samples, while the fluorescence microscopy-based assay exhibited better specificity for serum and overall higher reproducibility. High Spearman correlation values were calculated between HPV16-IgG and HPV16-neutralizing antibodies for both protocols (r s : 0.54–0.94, p < .001). Significant Spearman correlations between FVU and serum concentrations were also established for all assays (r s : 0.44–0.91, p < .01). This study demonstrates the continued neutralizing ability of antibodies captured with FVU, supporting the hypothesis that HPV vaccination may reduce autoinoculation and transmission risk to the sexual partner. Although further protocol optimizations are warranted, these findings provide a foundation for future research and larger cohort studies that could have implications for the optimal design, evaluation, and implementation of HPV vaccination programs.

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Molecular characterization of the cervical and systemic B-cell repertoire

Cited by 6 publications

References 74 publications

Natural Immunity to HIV: A Template for Vaccine Strategies

Natural Immunity to HIV: A Template for Vaccine Strategies

Blood B Lymphocyte Stimulator (BLyS)/BAFF levels may reflect natural immunity to HIV in highly exposed uninfected Beninese Commercial Sex Workers

HPV-specific antibodies in female genital tract secretions captured via first-void urine retain their neutralizing capacity

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