Allergic Reactivity and Memory Occur Independently of Sequential Switching Through IgG1

Allergic reactions to foods are primarily driven by allergen-binding immunoglobulin (Ig)E antibodies. IgE-expressing cells can be generated through direct switching from IgM to IgE or a sequential class switching pathway where activated B cells first switch to an intermediary isotype, most frequentl...

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Autores: Koenig, Joshua F.E., Wade-Vallance, Adam K., Jiménez-Saiz, Rodrigo, Bruton, Kelly, Gadkar, Siyon, Grydziuszko, Emily, Walker, Tina D., Gordon, Melissa E., Gillgrass, Amy E., Taylor, Justin J., Waserman, Susan, Jordana, Manel
Tipo de recurso: artículo
Fecha de publicación:2025
País:España
Institución:Universidad de Málaga
Repositorio:DDFV. Repositorio Institucional de la Universidad Francisco de Vitoria
Idioma:inglés
OAI Identifier:oai:ddfv.ufv.es:10641/6948
Acceso en línea:https://hdl.handle.net/10641/6948
Access Level:acceso abierto
Palabra clave:IgE
IgG1
memory
sensitization
sequential switching
Immunology and Allergy
Immunology
Journal Article
yes
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spelling Allergic Reactivity and Memory Occur Independently of Sequential Switching Through IgG1Koenig, Joshua F.E.Wade-Vallance, Adam K.Jiménez-Saiz, RodrigoBruton, KellyGadkar, SiyonGrydziuszko, EmilyWalker, Tina D.Gordon, Melissa E.Gillgrass, Amy E.Taylor, Justin J.Waserman, SusanJordana, ManelIgEIgG1memorysensitizationsequential switchingImmunology and AllergyImmunologyJournal ArticleyesAllergic reactions to foods are primarily driven by allergen-binding immunoglobulin (Ig)E antibodies. IgE-expressing cells can be generated through direct switching from IgM to IgE or a sequential class switching pathway where activated B cells first switch to an intermediary isotype, most frequently IgG1, and then to IgE. It has been proposed that sequential class switch recombination is involved in augmenting the severity of allergic reactions, generating high affinity IgE, differentiation of IgE plasma cells, and in holding the memory of IgE responses. We directly tested these possibilities by comparing the allergic immunity of wild-type and IgG1-deficient (hMT) mice. We found that sequential switching through IgG1 was not required to maintain the binding capacity of IgE nor for its ability to promote degranulation and elicit anaphylaxis against bona fide food allergens. Furthermore, the absence of sequential switching modestly impacted IgE affinity and clinical reactivity against hapten antigens, suggesting that the nature of the antigen impacts the requirement for sequential switching. At a cellular level, the capacity to undergo sequential switching through IgG1 provided no competitive advantage for subsequent IgE expression among germinal center B cells or plasma cells. Furthermore, the recall of allergic immunity at memory timepoints was preserved in the absence of sequential switching through IgG1, a finding that corresponded with intact type 2 memory B cell polarization. Together, these data demonstrate that sequential switching through IgG1 is redundant in sensitization, anaphylaxis, and the persistence of allergy, ultimately revealing that IgE derived from any switching source should be targeted by novel therapeutics seeking to ameliorate allergic diseases.Facultad de Ciencias Experimentales20252025-08-0120252025-08-01journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10641/6948reponame:DDFV. Repositorio Institucional de la Universidad Francisco de Vitoriainstname:Universidad de MálagaInglésengopen accesshttp://purl.org/coar/access_right/c_abf2http://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:ddfv.ufv.es:10641/69482026-06-11T12:44:57Z
dc.title.none.fl_str_mv Allergic Reactivity and Memory Occur Independently of Sequential Switching Through IgG1
title Allergic Reactivity and Memory Occur Independently of Sequential Switching Through IgG1
spellingShingle Allergic Reactivity and Memory Occur Independently of Sequential Switching Through IgG1
Koenig, Joshua F.E.
IgE
IgG1
memory
sensitization
sequential switching
Immunology and Allergy
Immunology
Journal Article
yes
title_short Allergic Reactivity and Memory Occur Independently of Sequential Switching Through IgG1
title_full Allergic Reactivity and Memory Occur Independently of Sequential Switching Through IgG1
title_fullStr Allergic Reactivity and Memory Occur Independently of Sequential Switching Through IgG1
title_full_unstemmed Allergic Reactivity and Memory Occur Independently of Sequential Switching Through IgG1
title_sort Allergic Reactivity and Memory Occur Independently of Sequential Switching Through IgG1
dc.creator.none.fl_str_mv Koenig, Joshua F.E.
Wade-Vallance, Adam K.
Jiménez-Saiz, Rodrigo
Bruton, Kelly
Gadkar, Siyon
Grydziuszko, Emily
Walker, Tina D.
Gordon, Melissa E.
Gillgrass, Amy E.
Taylor, Justin J.
Waserman, Susan
Jordana, Manel
author Koenig, Joshua F.E.
author_facet Koenig, Joshua F.E.
Wade-Vallance, Adam K.
Jiménez-Saiz, Rodrigo
Bruton, Kelly
Gadkar, Siyon
Grydziuszko, Emily
Walker, Tina D.
Gordon, Melissa E.
Gillgrass, Amy E.
Taylor, Justin J.
Waserman, Susan
Jordana, Manel
author_role author
author2 Wade-Vallance, Adam K.
Jiménez-Saiz, Rodrigo
Bruton, Kelly
Gadkar, Siyon
Grydziuszko, Emily
Walker, Tina D.
Gordon, Melissa E.
Gillgrass, Amy E.
Taylor, Justin J.
Waserman, Susan
Jordana, Manel
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Facultad de Ciencias Experimentales
dc.subject.none.fl_str_mv IgE
IgG1
memory
sensitization
sequential switching
Immunology and Allergy
Immunology
Journal Article
yes
topic IgE
IgG1
memory
sensitization
sequential switching
Immunology and Allergy
Immunology
Journal Article
yes
description Allergic reactions to foods are primarily driven by allergen-binding immunoglobulin (Ig)E antibodies. IgE-expressing cells can be generated through direct switching from IgM to IgE or a sequential class switching pathway where activated B cells first switch to an intermediary isotype, most frequently IgG1, and then to IgE. It has been proposed that sequential class switch recombination is involved in augmenting the severity of allergic reactions, generating high affinity IgE, differentiation of IgE plasma cells, and in holding the memory of IgE responses. We directly tested these possibilities by comparing the allergic immunity of wild-type and IgG1-deficient (hMT) mice. We found that sequential switching through IgG1 was not required to maintain the binding capacity of IgE nor for its ability to promote degranulation and elicit anaphylaxis against bona fide food allergens. Furthermore, the absence of sequential switching modestly impacted IgE affinity and clinical reactivity against hapten antigens, suggesting that the nature of the antigen impacts the requirement for sequential switching. At a cellular level, the capacity to undergo sequential switching through IgG1 provided no competitive advantage for subsequent IgE expression among germinal center B cells or plasma cells. Furthermore, the recall of allergic immunity at memory timepoints was preserved in the absence of sequential switching through IgG1, a finding that corresponded with intact type 2 memory B cell polarization. Together, these data demonstrate that sequential switching through IgG1 is redundant in sensitization, anaphylaxis, and the persistence of allergy, ultimately revealing that IgE derived from any switching source should be targeted by novel therapeutics seeking to ameliorate allergic diseases.
publishDate 2025
dc.date.none.fl_str_mv 2025
2025-08-01
2025
2025-08-01
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/10641/6948
url https://hdl.handle.net/10641/6948
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2

http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2

http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:DDFV. Repositorio Institucional de la Universidad Francisco de Vitoria
instname:Universidad de Málaga
instname_str Universidad de Málaga
reponame_str DDFV. Repositorio Institucional de la Universidad Francisco de Vitoria
collection DDFV. Repositorio Institucional de la Universidad Francisco de Vitoria
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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