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#36931600 2023/03/15 To Up
Single cell analysis of human nasal mucosal IgE antibody secreting cells reveals a newly minted phenotype.Immunoglobulin E (IgE) is central to the pathogenesis of allergic conditions including allergic fungal rhinosinusitis (AFRS). However, little is known about IgE antibody-secreting cells (ASCs). We performed single cell RNA sequencing (scRNA-seq) from CD19 and CD19 ASCs of nasal polyps (NPs) from patients with AFRS (n = 3). NPs were highly enriched in CD19 ASCs. Class-switched IgG and IgA ASCs were dominant (95.8%) while IgE ASCs were rare (2%) and found only in the CD19 compartment. Through immunoglobulin gene (VDJ) repertoire analysis, IgE ASCs shared clones with IgDCD27 "double negative" B cells, IgDCD27 unswitched memory B cells, and IgDCD27 switched memory B cells suggesting ontogeny from both IgD and memory B cells. Transcriptionally, mucosal IgE ASCs upregulated pathways related to antigen presentation, chemotaxis, B cell receptor stimulation, and survival when compared to non-IgE ASCs. IgE ASCs had higher expression of genes encoding LAPTM5 and CD23, as well as upregulation of CD74 (receptor for MIF), SARAF, and 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 compared to other class-switched mucosal ASCs and suggest unique functional roles for mucosal IgE ASCs in concert with immunoglobulin secretion.
Richard P Ramonell, Margaret Brown, Matthew C Woodruff, Joshua M Levy, Sarah K Wise, John DelGaudio, Meixue Duan, Celia L Saney, Shuya Kyu, Kevin S Cashman, Jennifer R Hom, Christopher F Fucile, Alexander F Rosenberg, Christopher M Tipton, Ignacio Sanz, Gregory C Gibson, F Eun-Hyung Lee