Igm Regulates Airway Hyperresponsiveness In Allergic Asthma Through Acetyl Choline Receptors

Abstract Allergic asthma is a disease driven by T helper 2 (TH2)-type cells secreting interleukin (IL-) 4, 5 and 13. It is characterized by eosinophils, airway hyperesponsiveness (AHR) and IgE secreting B cells. B cells play a role in allergic asthma in an allergen load dependent manner. IgM isotype secreted by naïve B cells is important for class switching. It is currently unclear how IgM isotype contributes in the development of allergic asthma. We investigated the role of IgM isotype in a house dust mite (HDM)-induced TH2 allergic asthma model. We sensitised wild type (wt), IgM-deficient (IgM−/−) and B cell-deficient (uMT−/−) mice with high (>10 ug) and low (<3 ug) dose of HDM extracts. We found IgM to be essential in antibody class switching and in AHR, but not in TH2 airway inflammation or eosinophilia. RNA seq suggested that IgM regulated AHR through modulating muscarinic receptor genes, particularly M3 and this was independent of microbiota. Transfer of wild type serum, but not B cells into IgM−/− mice could restore class switching but not AHR. These unprecedented findings suggest that IgM has a unique function in allergic asthma and regulates AHR by interacting with non-immune genes.