B cell-intrinsic MyD88 signaling is essential for IgE responses in lungs exposed to pollen allergens.

Allergen-specific IgE is linked to asthma pathogenesis, but the underlying mechanisms of IgE production in response to allergen exposure are poorly understood. In this article, we show that B cell-intrinsic MyD88 is essential for IgE/IgG1 production evoked by ragweed pollen instilled into lungs. MyD88-deficient mice showed defective IgE/IgG1 production and germinal center responses to lung instillation of ragweed pollen. However, MyD88 was dispensable for dendritic cell activation and Th2 cell development. B cell-specific deletion of MyD88 replicated the defective Ab production observed in MyD88-deficient mice. Although ragweed pollen contains TLR ligands, TLR2/4/9-deficient mice developed normal allergic responses to ragweed pollen. However, anti-IL-1R1 Ab-treated mice and IL-18-deficient mice showed decreased IgE/IgG1 production with normal Th2 development. Furthermore, B cell-specific MyD88-deficient mice showed reduced IgE/IgG1 production in response to lung instillation of OVA together with IL-1α, IL-1β, or IL-18. Thus, pollen instillation into lungs induces IL-1α/β and IL-18 production, which activates B cell-intrinsic MyD88 signaling to promote germinal center responses and IgE/IgG1 production.