Allergen-specific IgG+ memory B cells are temporally linked to IgE memory responses
| Autor: | Lars Harder Christensen, Ilka Hoof, Sara Herrera-de la Mata, Mohamed H. Shamji, Johanne Ahrenfeldt, Claus Lundegaard, Peter S. Andersen, Hanisah Sharif, Pandurangan Vijayanand, Björn Peters, Janice A. Layhadi, Esther Helen Steveling, Anders Lund, Jens Holm, Kristoffer Niss, Stephen R. Durham, Thomas Stranzl, Grégory Seumois, Veronique Schulten |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Allergy Immunology Somatic hypermutation plasmablasts medicine.disease_cause Immunoglobulin E 03 medical and health sciences 0302 clinical medicine Allergen memory B cells medicine Immunology and Allergy B cells Sublingual Immunotherapy biology Germinal center grass pollen allergy medicine.disease Isotype Basophil activation 030104 developmental biology 1107 Immunology biology.protein IGe Antibody 030215 immunology |
| Popis: | BACKGROUND: Immunoglobulin E (IgE) are least abundant, tightly regulated and IgE producing B cells are rare. The cellular origin and evolution of IgE responses are poorly understood.OBJECTIVE: To investigate the cellular and clonal origin of IgE memory responses following mucosal allergen exposure by sublingual immunotherapy (SLIT).METHODS: In a randomized double-blind, placebo-controlled, time-course SLIT study, peripheral blood mononuclear cells (PBMCs) and nasal biopsies were collected from forty adults with seasonal allergic rhinitis at baseline, 4, 8, 16, 28 and 52 weeks. RNA was extracted from PBMCs, sorted B cells and nasal biopsies for VH repertoire sequencing. Moreover, monoclonal antibodies were derived from single B cell transcriptomes.RESULTS: Combining VH repertoire sequencing and single cell transcriptomics yielded direct evidence of a parallel boost of two clonally and functionally related B cell subsets of short-lived IgE+ plasmablasts and IgG+ memory B cells (termed IgGE). Mucosal grass pollen allergen exposure by SLIT resulted in highly diverse IgE and IgGE repertoires. These were extensively mutated and appeared relative stable as per heavy chain isotype, somatic hypermutations and clonal composition. Single IgGE + memory B cell and IgE+ pre-plasmablast transcriptomes encoded antibodies that were specific for major grass pollen allergens and were able to elicit basophil activation at very low allergen concentrations.CONCLUSION: For the first time, we have shown that upon mucosal allergen exposure, human IgE memory resides in allergen-specific IgG+ memory B cells. These rapidly switch isotype and expand into short-lived IgE+ plasmablasts and serve as a potential target for therapeutic intervention. |
| Databáze: | OpenAIRE |
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