B cells under influence: transformation of B cells by Epstein–Barr virus

Küppers, Ralf

doi:10.1038/nri1201

Cited by 445 publications

(388 citation statements)

References 88 publications

Supporting

Mentioning

360

Contrasting

Unclassified

Order By: Relevance

“…In addition, transformation of EBV latency‐II‐expressing benign B cells may represent an initiating event in the pathogenesis of EBV + cHL. EBV‐infected germinal centre B cells have been shown to express the EBV latency‐II pattern 61, 62, identical to that seen in the HRS cells of EBV + cHL, which are known to have an atypical germinal centre derivation 63. In this situation, differential EBV latency‐II‐specific effector CD8 + T cell immune surveillance might contribute to the pathogenesis of EBV + cHL by attenuating immune‐mediated destruction of premalignant B cells.…”

Section: Discussionmentioning

confidence: 93%

The impact of HLA class I and EBV latency-II antigen-specific CD8+ T cells on the pathogenesis of EBV+ Hodgkin lymphoma

Jones

Wockner

Brennan

et al. 2015

Clinical and Experimental Immunology

View full text Add to dashboard Cite

SummaryIn 40% of cases of classical Hodgkin lymphoma (cHL), Epstein–Barr virus (EBV) latency‐II antigens [EBV nuclear antigen 1 (EBNA1)/latent membrane protein (LMP)1/LMP2A] are present (EBV+cHL) in the malignant cells and antigen presentation is intact. Previous studies have shown consistently that HLA‐A*02 is protective in EBV+cHL, yet its role in disease pathogenesis is unknown. To explore the basis for this observation, gene expression was assessed in 33 cHL nodes. Interestingly, CD8 and LMP2A expression were correlated strongly and, for a given LMP2A level, CD8 was elevated markedly in HLA‐A*02– versus HLA‐A*02+ EBV+cHL patients, suggesting that LMP2A‐specific CD8+ T cell anti‐tumoral immunity may be relatively ineffective in HLA‐A*02– EBV+cHL. To ascertain the impact of HLA class I on EBV latency antigen‐specific immunodominance, we used a stepwise functional T cell approach. In newly diagnosed EBV+cHL, the magnitude of ex‐vivo LMP1/2A‐specific CD8+ T cell responses was elevated in HLA‐A*02+ patients. Furthermore, in a controlled in‐vitro assay, LMP2A‐specific CD8+ T cells from healthy HLA‐A*02 heterozygotes expanded to a greater extent with HLA‐A*02‐restricted compared to non‐HLA‐A*02‐restricted cell lines. In an extensive analysis of HLA class I‐restricted immunity, immunodominant EBNA3A/3B/3C‐specific CD8+ T cell responses were stimulated by numerous HLA class I molecules, whereas the subdominant LMP1/2A‐specific responses were confined largely to HLA‐A*02. Our results demonstrate that HLA‐A*02 mediates a modest, but none the less stronger, EBV‐specific CD8+ T cell response than non‐HLA‐A*02 alleles, an effect confined to EBV latency‐II antigens. Thus, the protective effect of HLA‐A*02 against EBV+cHL is not a surrogate association, but reflects the impact of HLA class I on EBV latency‐II antigen‐specific CD8+ T cell hierarchies.

show abstract

Section: Discussionmentioning

confidence: 93%

The impact of HLA class I and EBV latency-II antigen-specific CD8+ T cells on the pathogenesis of EBV+ Hodgkin lymphoma

Jones

Wockner

Brennan

et al. 2015

Clinical and Experimental Immunology

View full text Add to dashboard Cite

show abstract

“…The pattern of expression of latent EBV-encoded genes in HRS indicates an important role for EBV in the rescue of these preapoptotic cells [8]. HRS cells exhibit type II latency, which includes LMP1, LMP2, EBNA1, and the EBERs (Fig.…”

Section: Ebv-associated B-cell Lymphoproliferative Disordersmentioning

confidence: 99%

“…In all variants, irrespective of the EBV status, constitutive activation of the c-myc oncogene through its translocation into one of the immunoglobulin loci is clearly the key factor in the oncogenesis of Burkitt lymphoma [41,42]. The detection of somatic hypermutations in the V region of the immunoglobulin genes and the phenotype of the Burkitt lymphoma cells indicate a GC cell origin of the lymphoma [8].…”

Section: Ebv-associated B-cell Lymphoproliferative Disordersmentioning

confidence: 99%

“…Although crippling mutations are also seen in classic Hodgkin lymphoma, HRS cells lack the intraclonal diversity because of the shutdown of the ongoing somatic mutations, in contrast to the EBV-infected B cells in AILT that continue to undergo somatic mutations even with the presence of crippling mutations [94]. The reasons for the sustained somatic hypermutation status are largely unknown, although it has been speculated by some that the rich FDRC meshwork and the increased number of CD4-positive helper T cells in AILT cases may stimulate the proliferating B cells to undergo somatic mutations and probably escape apoptosis [8].…”

Section: Ebv and T/nk-cell Lymphoproliferative Disordersmentioning

confidence: 99%

“…The virus is secreted in the saliva, and human infection occurs through oral transmission [6]. Oropharyngeal infection results in a lytic (productive) infection followed by infection of circulating B cells, leading to persistence of the viral DNA as an episome in the nucleus, thus establishing latent infection [7,8].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations