Defining the local tissue niche for resident memory B cells in allergic disease

Allergen (Ag)-specific IgE causes many of the symptoms we associate with allergy and asthma.

Despite the fact that we use ag-specific IgE as a diagnostic tool for allergic disease, it is not clear how IgE-levels are maintained in allergic individuals.

Accumulating evidence suggest that ag-specific IgG1+ memory B cells can undergo sequential switching, replenishing the pool of IgE+ plasma cells, but where this occurs is still elusive.

This proposal will explore the role for non-hematopoietic stromal cells (SCs) in creating a local niche for tissue-resident (TR) B cells in lungs permissive for sequential switching.

I will use 3D imaging as a primary tool to identify where TR B cells are localizing and complement this with in vivo and in vitro models to evaluate function.

Aim 1 will address the role for the alarmin IL-33 and how it can increase allergic sensitization and accumulation of TR B cells via activation of SCs.

Aim 2 will translate these findings to human tissue and explore equivalent subsets of SCs and TR B cells in healthy and allergic individuals.

Lastly, I aim to develop a novel tool for fateful polyclonal tracking of antigen-specific B cells in tissues for both imaging and functional applications, which has the potential to be used for a vast number of immunological models.

This proposal will advance our understanding of how local tissue-niches can influence chronic conditions such as allergic disease and pave the way for new intervention strategies.