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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.
Haematologica. 2006 Oct; 91(10):1313-20.H

Abstract

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.

Authors+Show Affiliations

Department of Pathology, Columbia University Medical Center, Columbia University, New York, NY 10032, USA. rshaknov@montefiore.orgNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17018379

Citation

Shaknovich, Rita, et al. "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." Haematologica, vol. 91, no. 10, 2006, pp. 1313-20.
Shaknovich R, Basso K, Bhagat G, et al. 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. Haematologica. 2006;91(10):1313-20.
Shaknovich, R., Basso, K., Bhagat, G., Mansukhani, M., Hatzivassiliou, G., Murty, V. V., Buettner, M., Niedobitek, G., Alobeid, B., & Cattoretti, G. (2006). 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. Haematologica, 91(10), 1313-20.
Shaknovich R, et al. 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. Haematologica. 2006;91(10):1313-20. PubMed PMID: 17018379.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Shaknovich,Rita, AU - Basso,Katia, AU - Bhagat,Govind, AU - Mansukhani,Mahesh, AU - Hatzivassiliou,Georgia, AU - Murty,Vundavalli V, AU - Buettner,Maike, AU - Niedobitek,Gerald, AU - Alobeid,Bachir, AU - Cattoretti,Giorgio, PY - 2006/10/5/pubmed PY - 2006/12/9/medline PY - 2006/10/5/entrez SP - 1313 EP - 20 JF - Haematologica JO - Haematologica VL - 91 IS - 10 N2 - 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. SN - 1592-8721 UR - https://www.unboundmedicine.com/medline/citation/17018379/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_ L2 - http://www.haematologica.org/cgi/pmidlookup?view=long&pmid=17018379 DB - PRIME DP - Unbound Medicine ER -