P05 (2026 - 2030) Control of human IgG4 B cells in tolerance-induction to aeroallergens

Guido Heine (CAU)

Project Summary 

Human IgG4 can inhibit IgE-mediated allergic reactions, which is relevant for the therapeutic effect of allergen immunotherapy (AIT). T follicular helper (Tfh) cell-derived IL-4 induces class switching to both IgE and IgG4. However, the mechanisms controlling the relative ratios of allergenic IgE and anti-allergenic IgG4 antibody subclasses relevant for allergy development and therapeutic efficacy of AIT are not known so far. Our preliminary studies suggest that IgG4 class switching follows a unique program, regulated at a defined step which dissects this from class switching to IgE. This projects will test this hypothesis, and aims to understand the induction of anti-allergenic B cells that will enable the development of targeting strategies to enhance the conversion of a type I allergic response into a non-allergic response and to generate rapid allergen-specific IgG4-driven memory response, without a long-lasting allergen immunotherapy.