Lung-resident IgG1⁺ memory B cells and IL-4-producing T_H2 cells mediate IgE responses in the airway

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Presentation Time: 02:15 PM - 03:30 PM
Poster Board Number: B136
Abstract ID: 5930

Presenting Author:
Alexander J Nelson , Postdoctoral Fellow at Loyola Univ. Chicago

Abstract:

Allergen-specific immunoglobulin E (IgE) mediates allergic diseases. B cells undergo class switch recombination (CSR) to IgE after cognate interactions with CD4⁺ T cells that produce IL-4 and CD40 ligand. However, the tissue sites and cell subsets that support IgE CSR are not fully understood.

We administered ragweed pollen and ovalbumin (OVA) intranasally to model allergic asthma in mice and observed the formation of lymphoid aggregates and memory B cells (MBCs) in the lungs. Using parabiosis, we found that MBCs are resident in the lungs and mediate OVA-specific IgE responses in the airway after OVA re-challenge.

Using fluorescent reporter mice, we found that IgE-switching B cells and IL-4-producing T cells were more frequent in the lungs than in the lung-draining lymph nodes (dLNs) or spleen. In the dLNs, germinal center B cells were the major IgE-switching subset and T follicular helper cells provided IL-4. In contrast, in the lungs, IgG1⁺ MBCs were the predominant IgE-switching cells and T_H2 cells produced IL-4. Co-culture experiments revealed that lung effector CD4⁺ T cells induced MBCs to undergo IgE CSR in an antigen and IL-4-dependent manner, suggesting that lung-infiltrating T_H2 cells drive elevated IgE CSR in the lungs.

These results identify the lung mucosa as the predominant site of IgE production and illustrate the differential regulation of IgE CSR between lymphoid and non-lymphoid tissues.