Allergen-specific IgG+ memory B cells are temporally linked to IgE memory responses
Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved..
BACKGROUND: IgE is the least abundant immunoglobulin and tightly regulated, and IgE-producing B cells are rare. The cellular origin and evolution of IgE responses are poorly understood.
OBJECTIVE: The cellular and clonal origin of IgE memory responses following mucosal allergen exposure by sublingual immunotherapy (SLIT) were investigated.
METHODS: In a randomized double-blind, placebo-controlled, time course SLIT study, PBMCs and nasal biopsy samples were collected from 40 adults with seasonal allergic rhinitis at baseline and at 4, 8, 16, 28, and 52 weeks. RNA was extracted from PBMCs, sorted B cells, and nasal biopsy samples for heavy chain variable gene repertoire sequencing. Moreover, mAbs were derived from single B-cell transcriptomes.
RESULTS: Combining heavy chain variable gene repertoire sequencing and single-cell transcriptomics yielded direct evidence of a parallel boost of 2 clonally and functionally related B-cell subsets of short-lived IgE+ plasmablasts and IgG+ memory B cells. Mucosal grass pollen allergen exposure by SLIT resulted in highly diverse IgE and IgGE repertoires. These were extensively mutated and appeared relatively stable as per heavy chain isotype, somatic hypermutations, and clonal composition. Single IgGE+ memory B-cell and IgE+ preplasmablast transcriptomes encoded antibodies that were specific for major grass pollen allergens and able to elicit basophil activation at very low allergen concentrations.
CONCLUSION: For the first time, we have shown that on mucosal allergen exposure, human IgE memory resides in allergen-specific IgG+ memory B cells. These cells rapidly switch isotype, expand into short-lived IgE+ plasmablasts, and serve as a potential target for therapeutic intervention.
| Errataetall: |
CommentIn: J Allergy Clin Immunol. 2020 Jul;146(1):77-79. - PMID 32413375 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:146 |
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| Enthalten in: |
The Journal of allergy and clinical immunology - 146(2020), 1 vom: 04. Juli, Seite 180-191 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Hoof, Ilka [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 02.03.2021 Date Revised 02.03.2021 published: Print-Electronic CommentIn: J Allergy Clin Immunol. 2020 Jul;146(1):77-79. - PMID 32413375 Citation Status MEDLINE |
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| doi: |
10.1016/j.jaci.2019.11.046 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM304838497 |
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| 245 | 1 | 0 | |a Allergen-specific IgG+ memory B cells are temporally linked to IgE memory responses |
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| 500 | |a Date Revised 02.03.2021 | ||
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| 500 | |a CommentIn: J Allergy Clin Immunol. 2020 Jul;146(1):77-79. - PMID 32413375 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a BACKGROUND: IgE is the least abundant immunoglobulin and tightly regulated, and IgE-producing B cells are rare. The cellular origin and evolution of IgE responses are poorly understood | ||
| 520 | |a OBJECTIVE: The cellular and clonal origin of IgE memory responses following mucosal allergen exposure by sublingual immunotherapy (SLIT) were investigated | ||
| 520 | |a METHODS: In a randomized double-blind, placebo-controlled, time course SLIT study, PBMCs and nasal biopsy samples were collected from 40 adults with seasonal allergic rhinitis at baseline and at 4, 8, 16, 28, and 52 weeks. RNA was extracted from PBMCs, sorted B cells, and nasal biopsy samples for heavy chain variable gene repertoire sequencing. Moreover, mAbs were derived from single B-cell transcriptomes | ||
| 520 | |a RESULTS: Combining heavy chain variable gene repertoire sequencing and single-cell transcriptomics yielded direct evidence of a parallel boost of 2 clonally and functionally related B-cell subsets of short-lived IgE+ plasmablasts and IgG+ memory B cells. Mucosal grass pollen allergen exposure by SLIT resulted in highly diverse IgE and IgGE repertoires. These were extensively mutated and appeared relatively stable as per heavy chain isotype, somatic hypermutations, and clonal composition. Single IgGE+ memory B-cell and IgE+ preplasmablast transcriptomes encoded antibodies that were specific for major grass pollen allergens and able to elicit basophil activation at very low allergen concentrations | ||
| 520 | |a CONCLUSION: For the first time, we have shown that on mucosal allergen exposure, human IgE memory resides in allergen-specific IgG+ memory B cells. These cells rapidly switch isotype, expand into short-lived IgE+ plasmablasts, and serve as a potential target for therapeutic intervention | ||
| 650 | 4 | |a Journal Article | |
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