Allergen inhalation transforms the lungs into a permissive environment for local IgE responses

Abstract Immunoglobulin E (IgE) is the primary cause of allergic diseases and must be tightly regulated. Production IgE occurs when activated B cells undergo class switch recombination (CSR) to IgE. These key events are rare, thus questions on which cell subsets CSR, where CSR predominantly occurs, molecular cellular signals promote remain unresolved. We modeled asthma by intranasal administration ragweed pollen ovalbumin (OVA) in mice, found that allergen inhalation induced formation lymphoid aggregates production OVA-specific lungs. Using fluorescent mice reporting switching, we revealed allergen-sensitized lungs were a major site with IgG1 +memory (MBCs) being dominant IgE-switching cells. Single-cell transcriptomics flow cytometry analyses tight correlation between CCR6 expression lung +MBCs, potentially explaining their recruitment/retention respiratory mucosa. Furthermore, lungMBCs underwent more frequentlythan MBCs draining lymph nodes or spleen. Since requires interleukin 4 (IL-4), used IL-4 reporter IL-4-producing T H2 enriched compared organs. Co-culture experiments using purified from splenic effector CD4 +T was elevated presence lungT cells, suggesting lung-infiltrating drive This study clarifies mucosa – environment supports +MBCs collaborating local responses. Supported grants NIH (F31 HL156459, T32 AI007508, R01 HL165120, R21 AI159456)