Single-cell analysis of human nasal mucosal IgE antibody secreting cells reveals a newly minted phenotype

Abstract

Immunoglobulin (Ig) E is central to the pathogenesis of allergic conditions, including allergic fungal rhinosinusitis. However, little is known about IgE antibody secreting cells (ASCs). We performed single-cell RNA sequencing from cluster of differentiation (CD)19⁺ and CD19^- ASCs of nasal polyps from patients with allergic fungal rhinosinusitis (n = 3). Nasal polyps were highly enriched in CD19⁺ ASCs. Class-switched IgG and IgA ASCs were dominant (95.8%), whereas IgE ASCs were rare (2%) and found only in the CD19⁺ compartment. Through Ig gene repertoire analysis, IgE ASCs shared clones with IgD^-CD27^- "double-negative" B cells, IgD⁺CD27⁺ unswitched memory B cells, and IgD^-CD27⁺ switched memory B cells, suggesting ontogeny from both IgD⁺ and memory B cells. Transcriptionally, mucosal IgE ASCs upregulate pathways related to antigen presentation, chemotaxis, B cell receptor stimulation, and survival compared with non-IgE ASCs. Additionally, IgE ASCs have a higher expression of genes encoding lysosomal-associated protein transmembrane 5 (LAPTM5) and CD23, as well as upregulation of CD74 (receptor for macrophage inhibitory factor), store-operated Calcium entry-associated regulatory factor (SARAF), and B cell activating factor receptor (BAFFR), which resemble an early minted ASC phenotype. Overall, these findings reinforce the paradigm that human ex vivo mucosal IgE ASCs have a more immature plasma cell phenotype than other class-switched mucosal ASCs and suggest unique functional roles for mucosal IgE ASCs in concert with Ig secretion.