Antibody-secreting B cells in HIV infection

Doria‐Rose, Nicole A.; Connors, Mark

doi:10.1097/coh.0b013e32832d9fac

Cited by 16 publications

(10 citation statements)

References 39 publications

(59 reference statements)

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“…Cross‐neutralizing antibodies, which are generated in up to 30% of infected people , emerge late, typically after about 2 years of infection (Fig. C) .…”

Section: Discussionmentioning

confidence: 99%

Independent evolution of Fc‐ and Fab‐mediated HIV‐1‐specific antiviral antibody activity following acute infection

et al. 2014

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Fc-related antibody activities, such as antibody-dependent cellular cytotoxicity (ADCC), or more broadly, antibody-mediated cellular viral inhibition (ADCVI), play a role in curbing early SIV viral replication, are enriched in human long-term infected non-progressors, and could potentially contribute to protection from infection. However, little is known about the mechanism by which such humoral immune responses are naturally induced following infection. Here we focused on the early evolution of the functional antibody response, largely driven by the Fc portion of the antibody, in the context of the evolving binding and neutralizing antibody response, which is driven mainly by the antibody binding fragment (Fab). We show that ADCVI/ADCC-inducing responses in humans are rapidly generated following acute HIV-1 infection, peak at approximately 6 months post-infection, but decay rapidly in the setting of persistent immune activation, as Fab-related activities persistently increase. Moreover, the loss of Fc activity occurred in synchrony with a loss of HIV-specific IgG3 responses. Our data strongly suggest that Fc- and Fab-related antibody functions are modulated in a distinct manner following acute HIV infection. Vaccination strategies intended to optimally induce both sets of antiviral antibody activities may, therefore, require a fine-tuning of the inflammatory response.

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“…Cross‐neutralizing antibodies, which are generated in up to 30% of infected people , emerge late, typically after about 2 years of infection (Fig. C) .…”

Section: Discussionmentioning

confidence: 99%

Independent evolution of Fc‐ and Fab‐mediated HIV‐1‐specific antiviral antibody activity following acute infection

et al. 2014

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“…Moreover, many fundamental questions remain unanswered. Enrichment of Jk2, Jk5 and V H 1 genes was observed in HIV-specific B-cells recovered from blood but no data is available regarding CNS cells (Doria-Rose and Connors, 2009). Somatic hypermutation, preferential mutational targeting of RGYW/WRCY motifs in the CDR of heavy chains (which is typically targeted by the enzyme activation-induced cytidine deaminase during the affinity maturation process), and the Replacement:Silent (R:S) ratio in CDR and FDR fragments (which are typical of antigendriven clonal selection) have not been studied in CNS B-cells to our knowledge and would be of major interest to demonstrate an intrathecal B-cell maturation process.…”

Section: Intrathecal Hiv-specific Igg Synthesis Is Frequently Observementioning

confidence: 99%

Compartmentalized intrathecal immunoglobulin synthesis during HIV infection — A model of chronic CNS inflammation?

Bonnan¹,

Barroso²,

Demasles³

et al. 2015

Journal of Neuroimmunology

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HIV infects the central nervous system (CNS) during primary infection and persists in resident macrophages. CNS infection initiates a strong local immune response that fails to control the virus but is responsible for by-stander lesions involved in neurocognitive disorders. Although highly active anti-retroviral therapy now offers an almost complete control of CNS viral proliferation, low-grade CNS inflammation persists. This review focuses on HIV-induced intrathecal immunoglobulin (Ig) synthesis. Intrathecal Ig synthesis early occurs in more than three-quarters of patients in response to viral infection of the CNS and persists throughout the course of the disease. Viral antigens are targeted but this specific response accounts for <5% of the whole intrathecal synthesis. Although the nature and mechanisms leading to non-specific synthesis are unknown, this prominent proportion is comparable to that observed in various CNS viral infections. Cerebrospinal fluid-floating antibody-secreting cells account for a minority of the whole synthesis, which mainly takes place in perivascular inflammatory infiltrates of the CNS parenchyma. B-cell traffic and lineage across the blood-brain-barrier have not yet been described. We review common technical pitfalls and update the pending questions in the field. Moreover, since HIV infection is associated with an intrathecal chronic oligoclonal (and mostly non-specific) Ig synthesis and associates with low-grade axonal lesions, this could be an interesting model of the chronic intrathecal synthesis occurring during multiple sclerosis.

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“…28,42 Second, Ag drives Ab production, [44][45][46] e.g., NAb titers are higher in people with elevated Ag levels than in long-term nonprogressors and effectively treated patients. 29,47,48 Third, Gag can be less abundant than Env, at least in lymph nodes. 49 An alternative explanation is that Env and Gag Ab responses are stimulated differently.…”

Section: Differential Responses To Gag and Envmentioning

confidence: 99%

“…For a more detailed discussion of HIV-1-induced B cell abnormalities and pathogenic mechanisms, other reviews should be consulted. 29,30 Hypergammaglobulinemia (hyper-GG) is a hallmark of untreated HIV-1 infection. 31,32 The excess IgG is directed against Ags from various microorganisms, including HIV-1, and some of it cross-reacts with autoantigens.…”

Section: The B Cell Response To Env In Hiv-1 Infectionmentioning

confidence: 99%

How Can HIV-Type-1-Env Immunogenicity Be Improved to Facilitate Antibody-Based Vaccine Development?

Klasse

Sanders

Cerutti

et al. 2012

AIDS Research and Human Retroviruses

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No vaccine candidate has induced antibodies (Abs) that efficiently neutralize multiple primary isolates of HIV-1. Preexisting high titers of neutralizing antibodies (NAbs) are essential, because the virus establishes infection before anamnestic responses could take effect. HIV-1 infection elicits Abs against Env, Gag, and other viral proteins, but of these only a subset of the anti-Env Abs can neutralize the virus. Whereas the corresponding proteins from other viruses form the basis of successful vaccines, multiple large doses of HIV-1 Env elicit low, transient titers of Abs that are not protective in humans. The inaccessibility of neutralization epitopes hinders NAb induction, but Env may also subvert the immune response by interacting with receptors on T cells, B cells, monocytes, macrophages, and dendritic cells. Here, we discuss evidence from immunizations of different species with various modified Env constructs. We also suggest how the divergent Ab responses to Gag and Env during infection may reflect differences in B cell regulation. Drawing on these analyses, we outline strategies for improving Env as a component of a vaccine aimed at inducing strong and sustained NAb responses.

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Antibody-secreting B cells in HIV infection

Abstract: Purpose of review-Several recent advances are permitting a detailed examination of the HIVspecific B cell response. In this review we summarize these advances and their implications for understanding the response to HIV in chronic infection or vaccinees.

Cited by 16 publications

References 39 publications

Independent evolution of Fc‐ and Fab‐mediated HIV‐1‐specific antiviral antibody activity following acute infection

Independent evolution of Fc‐ and Fab‐mediated HIV‐1‐specific antiviral antibody activity following acute infection

Compartmentalized intrathecal immunoglobulin synthesis during HIV infection — A model of chronic CNS inflammation?

How Can HIV-Type-1-Env Immunogenicity Be Improved to Facilitate Antibody-Based Vaccine Development?

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