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The Characterization of Epstein-Barr Virus Infected B Cells in the Peripheral Blood of Pediatric Solid Organ Transplant Recipients with Elevated Viral Loads

Schauer, Elizabeth M. (2005) The Characterization of Epstein-Barr Virus Infected B Cells in the Peripheral Blood of Pediatric Solid Organ Transplant Recipients with Elevated Viral Loads. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Abstract

Epstein-Barr virus (EBV) has infected 95% of the adult population. Yet, EBV stays as a harmless passenger in infected B-cells of nearly every host. EBV depends on a careful balance between the immune system and the virus that becomes evident when the host is immunocompromised. In such individuals, EBV can manifest as one of many associated malignancies. In children who have undergone solid organ transplantation, EBV-driven post-transplant lymphoproliferative disease (PTLD) can cause significant morbidity and mortality. We examined EBV-infected cells in non-diseased pediatric transplant recipients with elevated viral loads in their peripheral blood. Examination of high EBV genome copy cells in high load patients with a combined fluorescent in situ hybridization and immunofluorescence procedure demonstrated that the majority of high copy cells had no discernible expression of immunoglobulin on the surface (Ig-null cells). Such cells are lacking the crucial survival signal provided by an intact BCR and should not survive in the circulation. By flow cytometry, high load patients were shown to have the highest percentage of Ig-null cells in their peripheral blood; those with low viral loads and non-detectable viral loads had lower percentages. The phenotype of Ig-null cells was shown to differ from the resting memory B2 phenotype of normal latently infected B cells, with variable expression of CD20, CD40, and HLA Class I and II. Sorting Ig-null cells from the peripheral blood of high load carriers further demonstrated that in all patients examined, a large portion of the viral load was carried in the Ig-null compartment. Virus was also detected in the Ig-null, CD20- and HLA Class I- compartment, with a variable enrichment of the viral load in these compartments from patient to patient. Ig-null cells have been reported in the tumors of other EBV-associated malignancies, including PTLD, but never in the peripheral blood or in a non-disease state. This study has public health relevance because PTLD carries significant morbidity and mortality to transplant recipients; the presence in the blood of aberrant Ig-null cells which should have followed a program of apoptosis might be a risk factor for the development of PTLD or another EBV-associated disease.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Schauer, Elizabeth M.elizabeth.schauer@gmail.com
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairRowe, David Trowe1@pitt.eduROWE1
Committee MemberRinaldo, Charlesrinaldo@pitt.eduRINALDO
Committee MemberJenkins, Frankjenkins@pitt.eduJENKINS
Committee MemberWatkins, Simonswatkins@pitt.eduSWATKINS
Date: 9 June 2005
Date Type: Completion
Defense Date: 28 March 2005
Approval Date: 9 June 2005
Submission Date: 7 April 2005
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Institution: University of Pittsburgh
Schools and Programs: Graduate School of Public Health > Infectious Diseases and Microbiology
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: B cells; Epstein-Barr virus; Ig-null cells; post-transplant lymphoproliferative disease
Other ID: http://etd.library.pitt.edu/ETD/available/etd-04072005-123915/, etd-04072005-123915
Date Deposited: 10 Nov 2011 19:34
Last Modified: 15 Nov 2016 13:38
URI: http://d-scholarship.pitt.edu/id/eprint/6842

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