Lung memory B cells promote local IgE production in the respiratory tract

Autor: Alexander J Nelson, Yee Ling Wu
Rok vydání: 2022
Předmět:
Zdroj: The Journal of Immunology. 208:109.23-109.23
ISSN: 1550-6606
0022-1767
DOI: 10.4049/jimmunol.208.supp.109.23
Popis: Allergen-specific IgE mediates allergic asthma. IgE responses including class-switch recombination (CSR) to IgE are tightly regulated. However, the regulation of local CSR to IgE at mucosal sites is poorly understood. This study aims to elucidate cellular sources that promote IgE CSR and mechanisms that regulate IgE production in the respiratory tract. To model allergic airway inflammation, we repeatedly administered intranasal ragweed pollen and OVA to mice. We profiled B cell responses to OVA in the lung, the lung-draining mediastinal lymph nodes (medLN), spleen and bone marrow. We used fluorescent reporter mice to track IgE CSR and identify B cell subsets that promote IgE CSR by flow cytometry and microscopy. We found that intranasal allergen exposure elicited robust local B cell responses with the formation of OVA-specific B cells in the medLN and OVA-specific IgE in the airway. OVA-specific germinal center B cells and memory B cells (MBCs) accumulated in the lungs. Using fluorescent reporter mice, we showed that IgG1+ MBCs are the predominant IgE-switching cells. Importantly, the number of IgE-switching MBCs are the highest in the lungs, and IgG1+ MBCs exhibit an increased frequency of IgE CSR in the lungs compared to lymphoid tissues. These suggest that the lung environment favors IgE production. RNA-seq analyses comparing lung and circulating MBCs revealed elevated expression of Tnfsf4 (OX40L) and Icosl on lung MBCs, suggesting a higher propensity for lung MBCs to engage T cells. Together, these data demonstrate that the allergic lung is a major site of IgE CSR with IgG1+ MBCs promoting local IgE CSR. Our ongoing work focuses on delineating the B cell-intrinsic and extrinsic factors that promote IgE production in the respiratory mucosa. Supported by grants from NIH (1F31 HL156459, 5T32 AI007508, 1R21 AI159456)
Databáze: OpenAIRE
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