Allergic asthma is characterized by a Th2-dominated immune response associated with elevated

serum IgE levels in response to inhaled allergens, amongst which house dust mite (HDM) is the

most common. In this project, we want to characterize HDM-specific B cells in order to reveal

possible qualitative and quantitative differences between healthy and HDM-allergic individuals. To

study this, we will make use of a mouse model of HDM-induced allergic airway inflammation

(AAI) and of peripheral blood of healthy and HDM-allergic volunteers, some of the latter after

immunotherapy. We will first generate fluorescently labeled HDM proteins (derp1 and 2) to track

specific B cells. Then we will study HDM-specific B cells in terms of frequency, phenotype,

immunoglobulin isotypes and cytokines they produce both in mouse and humans. We are

particularly interested in HDM-specific IL-10-producing regulatory B cells (Breg). If we can

identify Breg in our mouse model, we will test their function in vitro by coculturing them with

HDM-specific T cells and in vivo by adoptively transferring them into mice that will subsequently

undergo the HDM AAI protocol. We will further address the need for B cells in AAI by running the

HDM protocol in B cell deficient mice. The proposed research could point the way towards

amplifying or inducing allergen-specific regulatory immunoglobulins and Bregs. This would have a

tremendous impact on the applicability of immunotherapy.