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Single-cell analysis of human nasal mucosal IgE antibody secreting cells reveals a newly minted phenotype.
Ramonell, Richard P; Brown, Margaret; Woodruff, Matthew C; Levy, Joshua M; Wise, Sarah K; DelGaudio, John; Duan, Meixue; Saney, Celia L; Kyu, Shuya; Cashman, Kevin S; Hom, Jennifer R; Fucile, Christopher F; Rosenberg, Alexander F; Tipton, Christopher M; Sanz, Ignacio; Gibson, Gregory C; Lee, F Eun-Hyung.
Affiliation
  • Ramonell RP; Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
  • Brown M; Georgia Institute of Technology, Atlanta, Georgia, USA.
  • Woodruff MC; Emory Autoimmunity Center of Excellence, Emory University, Atlanta, Georgia, USA; Department of Medicine, Division of Rheumatology, Lowance Center for Human Immunology, Emory University, Atlanta, Georgia, USA.
  • Levy JM; Department of Otolaryngology - Head and Neck Surgery, Emory University, Atlanta, Georgia, USA.
  • Wise SK; Department of Otolaryngology - Head and Neck Surgery, Emory University, Atlanta, Georgia, USA.
  • DelGaudio J; Department of Otolaryngology - Head and Neck Surgery, Emory University, Atlanta, Georgia, USA.
  • Duan M; Georgia Institute of Technology, Atlanta, Georgia, USA.
  • Saney CL; College of Veterinary Medicine, University of Georgia, Athens, Georgia, USA.
  • Kyu S; Department of Medicine, Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Emory University, Atlanta, Georgia, USA.
  • Cashman KS; Emory Autoimmunity Center of Excellence, Emory University, Atlanta, Georgia, USA; Department of Medicine, Division of Rheumatology, Lowance Center for Human Immunology, Emory University, Atlanta, Georgia, USA.
  • Hom JR; Emory Autoimmunity Center of Excellence, Emory University, Atlanta, Georgia, USA; Department of Medicine, Division of Rheumatology, Lowance Center for Human Immunology, Emory University, Atlanta, Georgia, USA.
  • Fucile CF; Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, USA; Informatics Institute, University of Alabama at Birmingham, Birmingham, Alabama, USA.
  • Rosenberg AF; Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama, USA; Informatics Institute, University of Alabama at Birmingham, Birmingham, Alabama, USA.
  • Tipton CM; Emory Autoimmunity Center of Excellence, Emory University, Atlanta, Georgia, USA; Department of Medicine, Division of Rheumatology, Lowance Center for Human Immunology, Emory University, Atlanta, Georgia, USA.
  • Sanz I; Emory Autoimmunity Center of Excellence, Emory University, Atlanta, Georgia, USA; Department of Medicine, Division of Rheumatology, Lowance Center for Human Immunology, Emory University, Atlanta, Georgia, USA.
  • Gibson GC; Georgia Institute of Technology, Atlanta, Georgia, USA.
  • Lee FE; Department of Medicine, Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Emory University, Atlanta, Georgia, USA. Electronic address: f.e.lee@emory.edu.
Mucosal Immunol ; 16(3): 287-301, 2023 06.
Article in En | MEDLINE | ID: mdl-36931600
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Nasal Polyps Limits: Humans Language: En Journal: Mucosal Immunol Year: 2023 Document type: Article
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Nasal Polyps Limits: Humans Language: En Journal: Mucosal Immunol Year: 2023 Document type: Article