Year: 2021
Type: article
Study design: Observational Study
Abstract: 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 H 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.
Source: Mucosal Immunology
Authors: Alessia Corrado, Richard P. Ramonell, Matthew C. Woodruff, Christopher Tipton, Sarah Wise, Joshua Levy, John DelGaudio, Merin E. Kuruvilla, Kelly R. Magliocca, Deepak Tomar, Swetha Garimalla, Christopher D. Scharer, Jeremy M. Boss, Hao Wu, Sanjeev Gumber, Chris Fucile, Greg Gibson, Alexander Rosenberg, Iñaki Sanz, F. Eun-Hyung Lee
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,480
Awards: Predoctoral Training Program in Genetics, G1189622924, Development of Clinical Trial Matching Engine Technology to Accelerate Participan, Understanding Survival of Human Bone Marrow Long-Lived Plasma Cells, Human IgE Antibody Secreting Cells in Blood, Nasal Polyps, and Bone Marrow, Immune Function and Biodefense in Children, Elderly, and the Immunocrompromised , G3588993705, G7022126505, A Model System for the Study of Human B-cell Tolerance, Characterization of a Novel Diagnostic Test for Pneumococcal Infection, B Cells in Health and Disease, G7741146425, Virus-induced Cell Fate Decisions in Anti-Viral Immunity, Pathogenesis of RSV disease in the Elderly, G8341471131, Plasma Cells in Health and Disease, Molecular Mechanisms of Human Long-lived Plasma Cell Generation in the Bone Marrow and Spleen, Molecular Analysis and Lineage Tracing of Influenza-Specific, Lung-Resident Memory B Cells, Georgia Clinical & Translational Science Alliance (Georgia CTSA), Regulation of B cell Responses in SLE and Other Autoimmune Diseases
OpenAlex ID: W3165189606