Metabolic regulation of immune responses during infection.

Effective immune responses during infection or vaccination require successful activation, differentiation and antibody production by B cells. A key mechanism controlling immune cell activation is cellular metabolism, as regulation of metabolic pathways influences fate choices and the functions of activated immune cells. While the metabolic pathways controlling B cell activation remain poorly understood, recent studies suggest a key role for lipid metabolism in the regulation of B cell responses. Accordingly, highly activated germinal centre B cells show a reprogramming of lipid metabolism with an increase in fatty acid oxidation; while impairment of lipid metabolism results in dysregulated B cell activation. Given the key role of B cells in protective immunity and autoimmune diseases, it is of central importance to understand how metabolic programs are regulated

Unpublished data from our lab demonstrate a unique function for the lipid presenting molecule CD1d in the regulation of cellular lipid metabolism. As CD1d is highly expressed on B cells, we aim to investigate the link between CD1d and B cell metabolism and how this in turn controls B cell activation and antibody production.

Aim of the investigation:

Investigating the mechanisms controlling B cell activation



Proposed plan of work:

Year 1/2. We will use a combination of next-generation sequencing and lipidomics to identify the molecular links between CD1 and lipid metabolism pathways in B cells

Year 2/3. We will take advantage of in vitro cultures and cellular and molecular biology techniques to manipulate lipid metabolism pathways and determine their effect on B cell responses

Year 3/4. We will use transgenic mice and in vivo models of vaccination to uncover the link between B cell metabolism and antibody production.