Unravelling fate determination in the allergic immune response

Allergic immune responses are directed by IgE antibody-producing cells. A new reservoir of IgE-producing cell precursors, type 2 memory B cells has recently been defined in mice and humans. Interestingly, while these cells are poised to produce IgE, they require activation by allergen and exposure to the cytokine IL-4 to become IgE antibody-producing cells (PC). I am interested in the level of regulation of IgE production by the cells. In this cellular immunology project, bait-and-switch experiments, and IL-4-inhibiting therapies will be used to determine whether type 2 memory B cells make the decision to become IgE PC based on T cell IL-4 provision and the priming of the T cell, or receive signals that drive differentiation in an IL-4 rich environment non-specifically. Ways to suppress IgE production will be investigated and disengaging the allergic predisposition of type 2 memory B cells from their realization of that fate will be attempted. Experience will be gained with mouse handling, B cell and T cell biology, allergic immune studies. Core technologies employed will be high dimension flow cytometry including spectral flow, immunizations and vaccines, adjuvant biology, click chemistry, RNAseq, scRNAseq and hapten-protein conjugation formation.