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Studies of EBV infection of B Lymphocytes ex Vivo and in Vitro

Heath, Emily (2011)
Ph.D. thesis, University of Birmingham.

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EBV is a lymphotropic herpesvirus that establishes lifelong persistence in the memory B cell compartment of the human host. It is still unclear, however, whether the virus infects memory B cells directly, or first targets naive B cells, driving them to differentiate into memory B cells via germinal centre (GC) transit. Using ex vivo analysis of sorted B cell subsets, we have found that whilst EBV preferentially colonises isotype-switched memory B cells, the virus was excluded from tonsillar GC B cells. Furthermore we found substantial viral loads in non-switched memory B cell populations, whose origins are likely to be germinal centre-independent. Using in vitro infection experiments, we showed that enzymes AID, UNG and pol-η, which are associated with the GC processes somatic hypermutation (SHM) and class switch recombination (CSR) were upregulated in EBV-infected B cells. Indeed following in vitro transformation, SHM of immunoglobulin (Ig) genes was induced in a proportion naive B cells. Whilst these cells did not undergo CSR following EBV infection alone, additional cytokine stimulation together with CD40L was able to induce isotype switching. EBV infection in vitro together with the provision of appropriate signals was therefore able to induce genotypic and phenotypic memory B cell characteristics in naive B cells, in a non-GC environment. Taken together our findings suggest that GC transit is not an essential requirement for EBV colonisation of the memory B cell population.

Type of Work:Ph.D. thesis.
Supervisor(s):Rowe, Martin and Bell, Andrew
School/Faculty:Colleges (2008 onwards) > College of Medical & Dental Sciences
Department:School of Cancer Studies
Subjects:RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Institution:University of Birmingham
ID Code:1714
This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder.
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