The influence of microRNAs and PrPc on the development and function of follicular dendritic cells
(Susan Aungier : collaboration with Neil Mabbot)
Follicular dendritic cells (FDCs) are found in the follicles of secondary lymphoid organs where they form complex network of dendritic processes. They use these dendritic processes to trap intact antigen in the form of immune complexes and display this to B lymphocytes. This facilitates antibody class-switching and the maintenance of memory to a particular antigen.
FDCs also express high levels of the cellular prion protein PrPc. During prion disease, PrPc is abnormally folded to a protease resistant form, termed PrPd. PrPd is found trapped in immune complexes on the surface of FDCs and it accumulates on FDCs in secondary lymphoid organs before moving to the brain and causing pathology.
This project aims to further our understanding of the development and function of FDCs by studying their microRNA profiles. To study the microRNA profiles of FDCs during differentiation we will utilise the dependence of FDCs status on signalling through the lyphotoxin-β receptor (LTβR). Signalling through the LTβR will be blocked using a LTβR- immunoglobulin fusion protein which causes rapid de-differentiation of FDCs. Recovery of the mature networks occurs over the 21 days following treatment. By comparing microRNA profiles of spleens with mature FDC networks, de-differentiating networks and de-differentiated networks we will be able to identify microRNAs, and thus genes, involved in FDC development. Similarly we will look for microRNAs which may be involved in the control of PrPc expression.