Genetic analysis of the role of the PI3K signalling in humoral immunity

Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

The B cell is a crucial component of the normal immune system, however its dysregulation can lead to certain types of leukaemia, lymphoma and myeloma. The importance of a regulatory network of transcription factors (proteins which bind to DNA to transfer information into RNA) controlling B cell identity and differentiation (specialisation) is well established. However, important mechanistic gaps in our knowledge remain. The role of signalling pathways in the regulation of B cell differentiation is clearly vital but remains poorly understood at the physiological level. In particular, we have limited knowledge of the signalling mechanisms that drive naive B cells to become germinal centre (GC) B cells and the signals that promote differentiation of GC B cells into the cell fates of memory versus plasma cells. We have obtained results to indicate the pathway that controls production of the lipid phosphatidylinositol-tris-phosphate (PIP3) plays an important role in B cell function. The levels of PIP3 are regulated by a relatively small family of kinases (enzymes that transfers phosphate groups to specific substrates) and phosphatases (enzymes that removes a phosphate group from substrates). This project seeks to exploit novel research tools to understand how B cell differentiation is regulated and to understand the importance of the PIP3 pathway in control of that process.

unavailable