Extrafollicular IgD+ B cells generate IgE antibody secreting cells in the nasal mucosa

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...

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Bibliographic Details
Published in:	Mucosal immunology 2021-09, Vol.14 (5), p.1144-1159
Main Authors:	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
Format:	Article
Language:	eng
Subjects:	Adult Allergic rhinitis Allergies Antibodies Antibody Formation - genetics Antibody Formation - immunology Antibody-Producing Cells - immunology Antibody-Producing Cells - metabolism Asthma B-Lymphocyte Subsets - immunology B-Lymphocyte Subsets - metabolism Bone marrow Class switching Computational Biology Connectivity Disease Gene Expression Profiling Germinal Center - immunology Germinal centers High-Throughput Nucleotide Sequencing Humans Hypersensitivity - etiology Hypersensitivity - metabolism Immunoglobulin A Immunoglobulin Class Switching - genetics Immunoglobulin Class Switching - immunology Immunoglobulin D Immunoglobulin D - immunology Immunoglobulin E Immunoglobulin E - immunology Immunoglobulin G Immunoglobulin Isotypes - genetics Immunoglobulin Isotypes - immunology Immunoglobulin M Immunology Immunophenotyping Lymphocytes B Medicine Mucosa Mutation Nasal Mucosa - immunology Nasal Mucosa - metabolism Nasal Polyps - etiology Nasal Polyps - metabolism Nasal Polyps - pathology Next-generation sequencing Pathogenesis Pollen - immunology Polyps Recombination Rhinitis Seasons Severe acute respiratory syndrome coronavirus 2 Somatic Hypermutation, Immunoglobulin Transcription
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Summary:	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 V next 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.
ISSN:	1933-0219 1935-3456