Epstein-Barr virus colonization of tonsillar and peripheral blood B-cell subsets in primary infection and persistence

Chaganti, Sridhar; Heath, Emily; Bergler, W.; Kuo, Michael; Buettner, Maike; Niedobitek, Gerald; Rickinson, Alan B.; Bell, Andrew I.

doi:10.1182/blood-2008-08-175828

Cited by 51 publications

(61 citation statements)

References 52 publications

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“…In summary, although we had anticipated that EBV might be present in the numerically dominant transitional and naive B-cell populations in allo-HSCT recipients, the present data argue that EBV is restricted to CD27 1 memory B cells, just as in immunocompetent individuals. 18,20 This is not to deny that EBV can For personal use only. on May 9, 2018.…”

Section: Discussionmentioning

confidence: 99%

“…Although posttransplant monitoring has led to an improvement in the early detection of patients at risk of developing PTLD, the pathophysiology of EBV reactivation in the context of allo-HSCT remains poorly understood. Given that memory B cells are the normal reservoir of EBV persistence in immunocompetent individuals, [18][19][20] we were particularly intrigued by existing reports in the literature that EBV reactivation following allo-HSCT usually occurs at a time when the newly reconstituting B-cell system consists predominantly of transitional and naive B cells. [21][22][23][24][25] To investigate this apparent paradox, here we have explored the relationship between immune reconstitution and EBV reactivation in a cohort of allo-HSCT recipients and ask whether the well-documented pattern of immune reconstitution [26][27][28] following allo-HSCT is perturbed in patients with high-level EBV reactivation.…”

Section: Introductionmentioning

confidence: 99%

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Memory B-cell reconstitution following allogeneic hematopoietic stem cell transplantation is an EBV-associated transformation event

Burns

Tierney

Shannon-Lowe

et al. 2015

Blood

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Key Points• CD191 CD27 1 memory B cells are detectable at supranormal frequencies in patients with high-level EBV DNAemia following allogeneic HSCT.• These memory B cells are frequently positive for EBV genomes and bear many of the hallmarks of lymphoblastoid transformation.Allogeneic stem cell transplantation (allo-HSCT) provides a unique opportunity to track Epstein-Barr virus (EBV) infection in the context of the reconstituting B-cell system. Although many allo-HSCT recipients maintain low or undetectable levels of EBV DNA posttransplant, a significant proportion exhibit elevated and rapidly increasing EBV loads which, if left untreated, may lead to potentially fatal EBV-associated posttransplant lymphoproliferative disease. Intriguingly, this high-level EBV reactivation typically arises in the first 3 months posttransplant, at a time when the peripheral blood contains low numbers of CD27 1 memory cells which are the site of EBV persistence in healthy immunocompetent donors. To investigate this apparent paradox, we prospectively monitored EBV levels and B-cell reconstitution in a cohort of allo-HSCT patients for up to 12 months posttransplant. In patients with low or undetectable levels of EBV, the circulating B-cell pool consisted predominantly of transitional and naive cells, with a marked deficiency of CD27 1 memory cells which lasted >12 months. However, among patients with high EBV loads, there was a significant increase in both the proportion and number of CD27 1 memory B cells. Analysis of sorted CD27 1 memory B cells from these patients revealed that this population was preferentially infected with EBV, expressed EBV latent transcripts associated with B-cell growth transformation, had a plasmablastic phenotype, and frequently expressed the proliferation marker Ki-67. These findings suggest that high-level EBV reactivation following allo-HSCT may drive the expansion of latently infected CD27 1 B lymphoblasts in the peripheral blood. (Blood. 2015;126(25):2665-2675

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Memory B-cell reconstitution following allogeneic hematopoietic stem cell transplantation is an EBV-associated transformation event

Burns

Tierney

Shannon-Lowe

et al. 2015

Blood

Self Cite

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“…IgD + CD27 + cells have been characterized as non-switched memory cells or marginal zone-like B cells (9,10). Healthy asymptomatic EBV carriers have low numbers of circulating EBV + B cells that are confined mainly to the IgD 2 CD27 + compartment but can also be found among IgD + CD27 + cells (11,12).…”

Section: E Pstein-barr Virus Infection Is Commonly Contracted Inmentioning

confidence: 99%

Cytomegalovirus-Seropositive Children Show Inhibition of In Vitro EBV Infection That Is Associated with CD8+CD57+ T Cell Enrichment and IFN-γ

Sohlberg

Saghafian–Hedengren

Rasul

et al. 2013

The Journal of Immunology

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EBV, a human herpesvirus, is commonly acquired during childhood and persists latently in B cells. EBV seropositivity has been connected to immunomodulatory effects such as altered T and NK cell functional responses as well as protection against early IgE sensitization; however, owing to the asymptomatic presentation during childhood little is known regarding the infection process in children of different ages. In this study, we used mononuclear cells from cord blood and from 2- and 5-y-old EBV-naive children for in vitro EBV infection. We show that the degree of EBV-induced B cell activation and expansion differs between age groups and in particular in relationship to IFN-γ production capacity. EBV infection induced redistribution between B cell subsets with enrichment of IgD+CD27+ cells (commonly referred to as non–switched memory) in infected cord blood cell cultures, and of IgD−CD27+ cells (switched memory) in cell cultures from older children. We also related results to serostatus to CMV, a persistent herpesvirus that can affect differentiation status of T and NK cells. As compared with CMV− children, the EBV-induced enrichment of IgD−CD27+ B cells was significantly reduced in infected cell cultures from CMV+ children. This effect was associated with high levels of IFN-γ and frequencies of highly mature CD8+CD57+ T cells in CMV+ children. Our results demonstrate that both a child’s age and serostatus to CMV will have an impact on EBV-induced B cell activation and expansion, and they point to the ability of viruses with immunomodulatory functions, such as CMV, to affect immune responses within the host system.

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“…Cells with the latter latency types are invisible for the immune system. Other studies suggested that during IM, the different EBV latency types are generated without entering the germinal centers (11)(12)(13). However, the details of this transition are not completely known.…”

mentioning

confidence: 99%

T Cells Modulate Epstein-Barr Virus Latency Phenotypes during Infection of Humanized Mice

Heuts

Rottenberg

Salamon

et al. 2014

J Virol

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Epstein-Barr virus colonization of tonsillar and peripheral blood B-cell subsets in primary infection and persistence

Abstract: Epstein-Barr virus (EBV) persists in the

Cited by 51 publications

References 52 publications

Memory B-cell reconstitution following allogeneic hematopoietic stem cell transplantation is an EBV-associated transformation event

Memory B-cell reconstitution following allogeneic hematopoietic stem cell transplantation is an EBV-associated transformation event

Cytomegalovirus-Seropositive Children Show Inhibition of In Vitro EBV Infection That Is Associated with CD8+CD57+ T Cell Enrichment and IFN-γ

T Cells Modulate Epstein-Barr Virus Latency Phenotypes during Infection of Humanized Mice

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