Sex Differences in Lung B Cell Responses in a Murine Model of Asthma.

INTRODUCTION: Asthma demonstrates a strong sex bias. B cells play critical roles in the pathogenesis of allergic inflammation, including allergen-specific immunoglobulin production. The sex-specific responses of B cell subsets in allergic lung inflammation remain unknown. This project aimed to study the sex differences in allergen-induced B cell subsets in a murine model of asthma. METHODS: Adult mice of both sexes were sensitized using two intraperitoneal injections of ovalbumin (OVA) on days 0 and 7. Mice were then challenged with intranasal OVA on days 14, 16, and 18 and euthanized 24 h after the last challenge. We examined whole-lung B-cell subsets using flow cytometry and whole-lung cytokine levels using ELISA or multiplex assay. RESULTS: OVA-treated female mice had significantly higher numbers of whole-lung naïve B cells and plasmablasts versus OVA-treated male mice. The numbers of IgM+ memory B cells and isotype-switched IgM- memory B cells in the lung trended higher in OVA-treated female mice. The lungs of OVA-treated female mice had increased C-C motif chemokine ligand 5, granulocyte-colony stimulating factor, IL-1β, and tumor necrosis factor-α protein levels, chemokines/cytokines involved in B-cell regulation, versus lungs from OVA-treated male mice. However, whole-lung B cell activating factor and a proliferation-inducing ligand levels showed no differences between male and female mice. CONCLUSIONS: In a murine asthma model, sex differences in whole-lung B lymphocytes are primarily driven by higher numbers of naïve B cells and plasmablasts in females versus males. Our results suggest that sex chromosomes and sex hormones may influence B-cell subsets during allergic lung inflammation.