Allergen-specific IgG+ memory B cells are temporally linked to IgE memory responses
Allergen-specific IgG+ memory B cells are temporally linked to IgE memory responses
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.
Hoof, Ilka
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Schulten, Veronique
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Layhadi, Janice A.
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Stranzl, Thomas
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Christensen, Lars H.
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de la Mata, Sara Herrera
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Seumois, Grégory
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Vijayanand, Pandurangan
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Lundegaard, Claus
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Niss, Kristoffer
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Lund, Anders
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Ahrenfeldt, Johanne
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Holm, Jens
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Steveling, Esther
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Sharif, Hanisah
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Durham, Stephen R.
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Peters, Björn
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Shamji, Mohamed H.
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Andersen, Peter S.
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Hoof, Ilka
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Schulten, Veronique
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Layhadi, Janice A.
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Stranzl, Thomas
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Christensen, Lars H.
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de la Mata, Sara Herrera
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Seumois, Grégory
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Vijayanand, Pandurangan
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Lundegaard, Claus
a29020e5-1617-40db-895c-8c7538d2787c
Niss, Kristoffer
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Lund, Anders
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Ahrenfeldt, Johanne
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Holm, Jens
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Steveling, Esther
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Sharif, Hanisah
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Durham, Stephen R.
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Peters, Björn
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Shamji, Mohamed H.
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Andersen, Peter S.
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Hoof, Ilka, Schulten, Veronique, Layhadi, Janice A., Stranzl, Thomas, Christensen, Lars H., de la Mata, Sara Herrera, Seumois, Grégory, Vijayanand, Pandurangan, Lundegaard, Claus, Niss, Kristoffer, Lund, Anders, Ahrenfeldt, Johanne, Holm, Jens, Steveling, Esther, Sharif, Hanisah, Durham, Stephen R., Peters, Björn, Shamji, Mohamed H. and Andersen, Peter S.
(2019)
Allergen-specific IgG+ memory B cells are temporally linked to IgE memory responses.
Journal of Allergy and Clinical Immunology.
(doi:10.1016/j.jaci.2019.11.046).
Abstract
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.
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Hoof_et_al_2019_JACI_revised_manuscript
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10.1016_j.jaci.2019.11.046
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Accepted/In Press date: 19 November 2019
e-pub ahead of print date: 27 December 2019
Identifiers
Local EPrints ID: 444256
URI: http://eprints.soton.ac.uk/id/eprint/444256
ISSN: 0091-6749
PURE UUID: 94bdaeac-f372-4750-9d2b-e9303ad27c62
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Date deposited: 06 Oct 2020 20:59
Last modified: 17 Mar 2024 05:12
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Contributors
Author:
Ilka Hoof
Author:
Veronique Schulten
Author:
Janice A. Layhadi
Author:
Thomas Stranzl
Author:
Lars H. Christensen
Author:
Sara Herrera de la Mata
Author:
Grégory Seumois
Author:
Pandurangan Vijayanand
Author:
Claus Lundegaard
Author:
Kristoffer Niss
Author:
Anders Lund
Author:
Johanne Ahrenfeldt
Author:
Jens Holm
Author:
Esther Steveling
Author:
Hanisah Sharif
Author:
Stephen R. Durham
Author:
Björn Peters
Author:
Mohamed H. Shamji
Author:
Peter S. Andersen
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