HIV-associated memory B cell perturbations

Hu, Zhiliang; Luo, Zhenwu; Wan, Zhuang; Wu, Hao; Li, Wei; Zhang, Tong; Jiang, Wei

doi:10.1016/j.vaccine.2015.04.008

Cited by 30 publications

(31 citation statements)

References 99 publications

(189 reference statements)

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“…In addition, many changes in the B cell compartment have been reported during HIV infection (reviewed in Refs. 85,86), namely, a reduction in resting memory and an increase in activated and tissue-like exhausted memory B cells subsets. A recent study has also demonstrated that vaccination against influenza A induces IgG-secreting cells in parallel with increases in CD21 2 CD27 + activated memory cells, as well as a reduction in tissue-like CD21 2 CD27 2 memory cells that were exhausted (87).…”

Section: Discussionmentioning

confidence: 99%

Identification of Vaccine-Altered Circulating B Cell Phenotypes Using Mass Cytometry and a Two-Step Clustering Analysis

Pejoski¹,

Tchitchek²,

Pozo³

et al. 2016

The Journal of Immunology

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Broadening our understanding of the abundance and phenotype of B cell subsets that are induced or perturbed by exogenous Ags will improve the vaccine evaluation process. Mass cytometry (CyTOF) is being used to increase the number of markers that can be investigated in single cells, and therefore characterize cell phenotype at an unprecedented level. We designed a panel of CyTOF Abs to compare the B cell response in cynomolgus macaques at baseline, and 8 and 28 d after the second homologous immunization with modified vaccinia virus Ankara. The spanning-tree progression analysis of density-normalized events (SPADE) algorithm was used to identify clusters of CD20+ B cells. Our data revealed the phenotypic complexity and diversity of circulating B cells at steady-state and significant vaccine-induced changes in the proportions of some B cell clusters. All SPADE clusters, including those altered quantitatively by vaccination, were characterized phenotypically and compared using double hierarchical clustering. Vaccine-altered clusters composed of previously described subsets including CD27hiCD21lo activated memory and CD27+CD21+ resting memory B cells, and subphenotypes with novel patterns of marker coexpression. The expansion, followed by the contraction, of a single memory B cell SPADE cluster was positively correlated with serum anti-vaccine Ab titers. Similar results were generated by a different algorithm, automatic classification of cellular expression by nonlinear stochastic embedding. In conclusion, we present an in-depth characterization of B cell subphenotypes and proportions, before and after vaccination, using a two-step clustering analysis of CyTOF data, which is suitable for longitudinal studies and B cell subsets and biomarkers discovery.

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Section: Discussionmentioning

confidence: 99%

Identification of Vaccine-Altered Circulating B Cell Phenotypes Using Mass Cytometry and a Two-Step Clustering Analysis

Pejoski¹,

Tchitchek²,

Pozo³

et al. 2016

The Journal of Immunology

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“…HIV dysregulates many aspects of TB immunity by causing chronic immune activation (18), skewing the T reg /T H 17 balance (19), and perturbing B-cell signaling and memory formation (20). HIV further blocks TNF-α-mediated macrophage activation and apoptosis, thus favoring the persistence of Mtb (21).…”

Section: Nonhuman Primate | B Cells | Tuberculosis | Cd4 T Cells | CDmentioning

confidence: 99%

CD4 ⁺ T-cell–independent mechanisms suppress reactivation of latent tuberculosis in a macaque model of HIV coinfection

Foreman

Mehra

LoBato

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

120

202

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The synergy between Mycobacterium tuberculosis (Mtb) and HIV in coinfected patients has profoundly impacted global mortality because of tuberculosis (TB) and AIDS. HIV significantly increases rates of reactivation of latent TB infection (LTBI) to active disease, with the decline in CD4 + T cells believed to be the major causality. In this study, nonhuman primates were coinfected with Mtb and simian immunodeficiency virus (SIV), recapitulating human coinfection. A majority of animals exhibited rapid reactivation of Mtb replication, progressing to disseminated TB and increased SIV-associated pathology. Although a severe loss of pulmonary CD4 + T cells was observed in all coinfected macaques, a subpopulation of the animals was still able to prevent reactivation and maintain LTBI. Investigation of pulmonary immune responses and pathology in this cohort demonstrated that increased CD8 + memory T-cell proliferation, higher granzyme B production, and expanded B-cell follicles correlated with protection from reactivation. Our findings reveal mechanisms that control SIV-and TB-associated pathology. These CD4-independent protective immune responses warrant further studies in HIV coinfected humans able to control their TB infection. Moreover, these findings will provide insight into natural immunity to Mtb and will guide development of novel vaccine strategies and immunotherapies.Nonhuman primate | B cells | tuberculosis | CD4 T cells | CD8 T cells

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“…However, this hypothesis is dissatisfying for several reasons. First, PEL, like MCD, is highly linked to HIV disease, which, even when well controlled by antiretroviral therapy (ART), is associated with defects in the GC reaction and the depletion of memory B cells [18]; events which would reduce the number and viability of memory B cells as infection targets in the early stages of PEL pathogenesis. Moreover, this hypothesis requires the supposition that KSHV has distinct biological effects leading to different disease states based on the target B cell subtype.…”

Section: Extrafollicular Maturation: Unifying the Viral Pathogenic Modelmentioning

confidence: 99%

Extrafollicular activities: perspectives on HIV infection, germinal center-independent maturation pathways, and KSHV-mediated lymphoproliferation

Totonchy

2017

Current Opinion in Virology

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Early events in the pathogenesis of KSHV-associated lymphoproliferations in the context of HIV disease remain poorly understood. Recent research indicates that latent HIV infection causes persistent immune dysfunction in B cell follicles. Simultaneously, lack of T cell immune surveillance in the lymph nodes disregulates the biology of EBV. In sum, these defects bias B lymphocyte maturation away from traditional T cell-dependent germinal center-mediated pathways and towards extrafollicular pathways. Recent advances in B lymphocyte immunology suggest that extrafollicular maturation pathways for antibody secreting cells are more flexible and robust than previously believed. These responses are now understood to be both durable and antigen-specific, and even canonically germinal center-restricted events such as class switch recombination and somatic hypermutation have now been demonstrated in an extrafollicular context. As a lymphotrophic pathogen which causes disease primarily in the context of HIV and EBV co-infection, future studies examining the interactions of KSHV biology with extrafollicular B cell maturation pathways will be critical to uncovering key aspects of KSHV-mediated immune pathology.

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HIV-associated memory B cell perturbations

Cited by 30 publications

References 99 publications

Identification of Vaccine-Altered Circulating B Cell Phenotypes Using Mass Cytometry and a Two-Step Clustering Analysis

Identification of Vaccine-Altered Circulating B Cell Phenotypes Using Mass Cytometry and a Two-Step Clustering Analysis

CD4 ⁺ T-cell–independent mechanisms suppress reactivation of latent tuberculosis in a macaque model of HIV coinfection

Extrafollicular activities: perspectives on HIV infection, germinal center-independent maturation pathways, and KSHV-mediated lymphoproliferation

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HIV-associated memory B cell perturbations

Cited by 30 publications

References 99 publications

Identification of Vaccine-Altered Circulating B Cell Phenotypes Using Mass Cytometry and a Two-Step Clustering Analysis

Identification of Vaccine-Altered Circulating B Cell Phenotypes Using Mass Cytometry and a Two-Step Clustering Analysis

CD4 + T-cell–independent mechanisms suppress reactivation of latent tuberculosis in a macaque model of HIV coinfection

Extrafollicular activities: perspectives on HIV infection, germinal center-independent maturation pathways, and KSHV-mediated lymphoproliferation

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CD4 ⁺ T-cell–independent mechanisms suppress reactivation of latent tuberculosis in a macaque model of HIV coinfection