Allergic Sensitization to Inhalant Allergens in the Upper Respiratory Tract—the B Cell Side

Allergic diseases are on the rise worldwide, driven by respiratory epithelial barrier dysfunction that promotes sensitization to inhalant allergens such as pollen, dust mites, pet dander, and fungal spores. These antigens trigger IgE-mediated immune responses that lead to diseases such as allergic rhinitis (AR) and asthma. B cells play a central role by producing allergen-specific IgE, presenting antigens, releasing cytokines, and forming memory B cells (MBCs). Their differentiation into IgE-secreting plasma cells (PCs) mainly relies on T cell help, germinal center (GC) reactions, and/or extrafollicular responses and class switch recombination (CSR), which makes them important therapeutic targets. The nasal mucosa, as the first point of contact for allergens, acts both as a barrier and as an immunological site. In AR, IL-13-driven goblet cell hyperplasia and overproduction of mucus compromise the integrity of the barrier. Although the nasal microbiome can influence the immune response, its role in atopy remains unclear. Local B cell activity, including extrafollicular IgE production and ectopic GCs, enhances mucosal immunity. Epithelial cells detect allergens via pattern recognition receptors (PRRs) and release alarmins (IL-25, IL-33, TSLP), which can trigger type 2 inflammation. Proteases from allergens such as house dust mites (HDM) disrupt epithelial junctions, while pollutants, smoke, microplastics, and allergen-derived metabolites further modulate immune activation. Allergens are transported to the lymph nodes by the passive flow to follicular dendritic cells (FDCs) or by active uptake by interferon regulatory factor (IRF) 4-dependent conventional type 2 DCs, which activate T follicular helper (TFH) cells to drive IgE responses. Advanced lymphoid organoids that mimic the microenvironment of GCs offer promising models for the study of allergic sensitization but require improved standardization.

Universität zu Lübeck
Medizinische Universität Wien - AKH
Karl Landsteiner Privatuniversität für Gesundheitswissenschaften GmbH