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The role of NF-kB2 in secondary and tertiary lymphoid tissue development

Mader, Emma (2011)
Ph.D. thesis, University of Birmingham.

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The role of the alternative NF-\(\kappa\)B pathway in the development of secondary lymphoid organs (SLOs) has been well described. Tertiary lymphoid organs (TLOs) include intestinal cryptopatches (CPs) and isolated lymphoid follicles (ILFs). This thesis investigates the role of the alternative NF-\(\kappa\)B pathway in the development of colonic ILFs, using the p100\(\Delta\) mouse model, where the alternative pathway is constitutively active. We present compelling data that p100\(\Delta\) mice develop significantly more lymphoid aggregates in the colon, compared with WT littermates, and provide several lines of evidence showing that these aggregates are analogous to ILFs. Additionally, we demonstrate that in the p100\(\Delta\) a significant increase in the numbers of B and T cells, and DCs in the colon and show alterations in the subsets of colonic T cells and DCs. We also present evidence that constitutively active NF-\(\kappa\)B2 p100 in LT\(\alpha\) deficient mice induces recovery of B and T cell segregation in the spleen. Most strikingly, we show recovery of iLNs and mLN development in one of five \(p100\)\(\Delta\)\(LT\)\(\alpha^{-/-}\) mice generated. These findings demonstrate that the alternative NF-\(\kappa\)B pathway plays an important role in not only SLO development and splenic organisation, but also in the development of TLOs, specifically colonic ILFs.

Type of Work:Ph.D. thesis.
Supervisor(s):Caamano, Jorge
School/Faculty:Colleges (2008 onwards) > College of Medical & Dental Sciences
Department:School of Immunity and Infection
Subjects:QR180 Immunology
Institution:University of Birmingham
ID Code:1608
This unpublished thesis/dissertation is copyright of the author and/or third parties.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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