eTheses Repository

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

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.