دورية
Extrafollicular IgD+ B cells generate IgE antibody secreting cells in the nasal mucosa
| العنوان: | Extrafollicular IgD+ B cells generate IgE antibody secreting cells in the nasal mucosa |
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| المؤلفون: | Corrado, Alessia, Ramonell, Richard P., Woodruff, Matthew C., Tipton, Christopher, Wise, Sarah, Levy, Joshua, DelGaudio, John, Kuruvilla, Merin E., Magliocca, Kelly R., Tomar, Deepak, Garimalla, Swetha, Scharer, Christopher D., Boss, Jeremy M., Wu, Hao, Gumber, Sanjeev, Fucile, Chris, Gibson, Greg, Rosenberg, Alexander, Sanz, Iñaki, Lee, F. Eun-Hyung |
| المصدر: | Mucosal immunology; September 2021, Vol. 14 Issue: 5 p1144-1159, 16p |
| مستخلص: | Increased IgE is a typical feature of allergic rhinitis. Local class-switch recombination has been intimated but B cell precursors and mechanisms remain elusive. Here we describe the dynamics underlying the generation of IgE-antibody secreting cells (ASC) in human nasal polyps (NP), mucosal tissues rich in ASC without germinal centers (GC). Using VHnext generation sequencing, we identified an extrafollicular (EF) mucosal IgD+ naïve-like intermediate B cell population with high connectivity to the mucosal IgE ASC. Mucosal IgD+ B cells, express germline epsilon transcripts and predominantly co-express IgM. However, a small but significant fraction co-express IgG or IgA instead which also show connectivity to ASC IgE. Phenotypically, NP IgD+ B cells display an activated profile and molecular evidence of BCR engagement. Transcriptionally, mucosal IgD+ B cells reveal an intermediate profile between naïve B cells and ASC. Single cell IgE ASC analysis demonstrates lower mutational frequencies relative to IgG, IgA, and IgD ASC consistent with IgE ASC derivation from mucosal IgD+ B cell with low mutational load. In conclusion, we describe a novel mechanism of GC-independent, extrafollicular IgE ASC formation at the nasal mucosa whereby activated IgD+ naïve B cells locally undergo direct and indirect (through IgG and IgA), IgE class switch. |
| قاعدة البيانات: | Supplemental Index |
Full Text Finder | تدمد: | 19330219 19353456 |
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| DOI: | 10.1038/s41385-021-00410-w |