Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Shaknovich, R. et al.

Shaknovich, Basso, Bhagat, Mansukhani, Hatzivassiliou, Murty, Buettner, Niedobitek, Alobeid, Cattoretti,

Identification of rare Epstein-Barr virus infected memory B cells and plasma cells in non-monomorphic post-transplant lymphoproliferative disorders and the signature of viral signaling.

BACKGROUND AND OBJECTIVES: In early and polymorphic post-transplant lymphoproliferative disorders (PTLD) Epstein-Barr virus (EBV), through its latency proteins, drives the proliferation of B lymphocytes, a process which in immunocompetent individuals leads to the establishment of latently infected memory B cells. DESIGN AND METHODS: We analyzed 11 cases, which included early and polymorphic PTLD, and 12 controls for latency of EBV infection and their antigenic profile. RESULTS: We identified a minority of terminally differentiated EBER+ IRTA1+ memory B cells and EBER+ CD138+ PRDM1+ plasma cells in these samples. These elements were identified both in PTLD and in tumor-free tonsils from post-transplant patients but not in EBV- control tonsils. The expression of EBV latency proteins is heterogeneous, and is associated with activation of the NF-kB pathway. EBV signaling (through EBNA2, LMP1 and LMP2A) and NF-kB activation correlated with upregulation of target proteins: cMYC, JunB, CCL22, TRAF1 and IRF4. EBV-infected lymphocytes in early and polymorphic PTLDs represent a mixture of latencies II, III and, in at least 1/3 of infected cells, of latency 0. INTERPRETATION AND CONCLUSIONS: EBV infection correlates with NF-kB activation, with EBV-dependent cell signaling, and lastly, with the presence of EBV-infected plasma cells and memory cells.[1]

References

Identification of rare Epstein-Barr virus infected memory B cells and plasma cells in non-monomorphic post-transplant lymphoproliferative disorders and the signature of viral signaling. Shaknovich, R., Basso, K., Bhagat, G., Mansukhani, M., Hatzivassiliou, G., Murty, V.V., Buettner, M., Niedobitek, G., Alobeid, B., Cattoretti, G. Haematologica (2006) [Pubmed]

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