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The exploitation of neuronal survival factors in Burkitt’s lymphoma and germinal centre B cells

Chirimuuta, Fungai Natalie Winnie (2010)
Ph.D. thesis, University of Birmingham.

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Abstract

Neurotrophins are neuromodulatory proteins utilised within neuronal networks for development and survival. Based on previous evidence revealing the expression of neurotrophin components in immune cells, the present study investigates neurotrophin component expression within Burkitt’s Lymphoma B cells. Different latency stages within Burkitt’s Lymphoma B cells are observed due to the expression of resident EBV latency genes. These B cells are said to display germinal centre B cell markers and interact with other cells within a germinal centre environment, such as Follicular Dendritic Cells (FDCs) and T cells. EBV latency phenotypes were characterised for the lines used here; these lines were then screened for the expression of neurotrophin ligands and their receptors: the selective high affinity Tropomyosin receptor kinases TrkA, TrkB and TrkC and the (common) low affinity, tumour necrosis factor receptor member, p75NTR. FDC-like cell lines were also analysed for neurotrophin component expression. This was to question FDCs as potential providers of paracrine neurotrophin signalling to Burkitt’s lymphoma B cells. Neurotrophin and neurotrophin receptor expression was detected by flow cytometry, confocal microscopy, reverse transcription polymerase chain reaction (PCR) and real time PCR methods. Cell lines with the full complement of EBV latency genes expressed were positive for the neurotrophin, Brain Derived Neurotrophic Factor (BDNF) and all neurotrophin receptors in question. Burkitt’s lymphoma cells expressing limited EBV latency genes revealed more restricted expression of neurotrophin components. FDC-like lines also express neurotrophin and neurotrophin receptors, thus paracrine signalling between Burkitt’s lymphoma cells and FDCs may occur via this axis, perhaps to enhance B cell survival.

Type of Work:Ph.D. thesis.
Supervisor(s):Gordon, John
School/Faculty:Colleges (2008 onwards) > College of Medical & Dental Sciences
Department:School of immunity and infection
Subjects:R Medicine (General)
Institution:University of Birmingham
ID Code:930
This unpublished thesis/dissertation is copyright of the author and/or third parties.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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