title: B cell-intrinsic MyD88 signaling is essential for IgE responses in lungs exposed to pollen allergens.
abstract: 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.
authors.affiliation: Laboratory of Allergic Diseases, Institute for Advanced Medical Sciences, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan; and.
authors.forename: Kazufumi
authors.initials: K
authors.lastname: Matsushita
authors.affiliation: Laboratory of Allergic Diseases, Institute for Advanced Medical Sciences, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan; and Department of Immunology and Medical Zoology, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan tomo@hyo-med.ac.jp.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Yoshimoto
mesh_terms: D000485:Allergens / Q000276:immunology; D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D052179:Antigens, Plant / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D016207:Cytokines / Q000096:biosynthesis; D007073:Immunoglobulin E / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology; D008168:Lung / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism*; D010936:Plant Extracts / Q000276:immunology; D011058:Pollen / Q000276:immunology*; D015398:Signal Transduction; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000235:genetics / Q000378:metabolism
chemical_list: D000485:Allergens; D052179:Antigens, Plant; D016207:Cytokines; D007074:Immunoglobulin G; D053594:Myeloid Differentiation Factor 88; D010936:Plant Extracts; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051217:Toll-Like Receptor 9; C433085:ragweed pollen; D007073:Immunoglobulin E