Naturally occurring mutation affecting the MyD88-binding site of TNFRSF13B impairs triggering of class switch recombination

Autores
Almejún, María Belén; Cols, Montserrat; Zelazko, Marta; Oleastro, Matías; Cerutti, Andrea; Oppezzo, Pablo; Cunningham Rundles, Charlotte; Danielian, Silvia
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Mutations in the transmembrane activator and calcium-modulating cyclophilin ligand interactor (TACI) were previously found to be associated with hypogammaglobulinemia in humans. It has been shown that proliferation inducing ligand (APRIL) elicits class switch recombination (CSR) by inducing recruitment of MyD88 to a TACI highly conserved cytoplasmic domain (THC). We have identified a patient with hypogammaglobulinemia carrying a missense mutation (S231R) predicted to affect the THC. Aiming to evaluate the relevance of this novel mutation of TACI in CSR induction, we tested the ability of TACI, TLR9, or/and CD40 ligands to trigger CSR in naive B cells and B-cell lines carrying S231R. IgG secretion was impaired when triggered by TACI or/and TLR9 ligands on S231R-naive B cells. Likewise, these stimuli induced less expression of activation-induced cytidine deaminase, I(γ)1-C(μ), and I(γ)1-C(μ), while induction by optimal CD40 stimulation was indistinguishable from controls. These cells also showed an impaired cooperation between TACI and TLR9 pathways, as well as a lack of APRIL-mediated enhancement of CD40 activation in suboptimal conditions. Finally, after APRIL ligation, S231R-mutated TACI failed to colocalize with MyD88. Collectively, these results highlight the requirement of an intact MyD88-binding site in TACI to trigger CSR.
Fil: Almejún, María Belén. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Laboratorio de Investigación; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Cols, Montserrat. Mount Sinai School of Medicine. Department of Medicine; Estados Unidos
Fil: Zelazko, Marta. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Laboratorio de Investigación; Argentina
Fil: Oleastro, Matías. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Laboratorio de Investigación; Argentina
Fil: Cerutti, Andrea. Mount Sinai School of Medicine. Department of Medicine; Estados Unidos
Fil: Oppezzo, Pablo. Instituto Pasteur. Unidad de Proteínas Recombinantes; Uruguay
Fil: Cunningham Rundles, Charlotte. Mount Sinai School of Medicine. Department of Medicine; Estados Unidos
Fil: Danielian, Silvia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Laboratorio de Investigación; Argentina
Materia
Class Switch Recombination
Myd88
Common Variable Immunodeficiency
Taci
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/3243
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/3243
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Naturally occurring mutation affecting the MyD88-binding site of TNFRSF13B impairs triggering of class switch recombinationAlmejún, María BelénCols, MontserratZelazko, MartaOleastro, MatíasCerutti, AndreaOppezzo, PabloCunningham Rundles, CharlotteDanielian, SilviaClass Switch RecombinationMyd88Common Variable ImmunodeficiencyTacihttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Mutations in the transmembrane activator and calcium-modulating cyclophilin ligand interactor (TACI) were previously found to be associated with hypogammaglobulinemia in humans. It has been shown that proliferation inducing ligand (APRIL) elicits class switch recombination (CSR) by inducing recruitment of MyD88 to a TACI highly conserved cytoplasmic domain (THC). We have identified a patient with hypogammaglobulinemia carrying a missense mutation (S231R) predicted to affect the THC. Aiming to evaluate the relevance of this novel mutation of TACI in CSR induction, we tested the ability of TACI, TLR9, or/and CD40 ligands to trigger CSR in naive B cells and B-cell lines carrying S231R. IgG secretion was impaired when triggered by TACI or/and TLR9 ligands on S231R-naive B cells. Likewise, these stimuli induced less expression of activation-induced cytidine deaminase, I(γ)1-C(μ), and I(γ)1-C(μ), while induction by optimal CD40 stimulation was indistinguishable from controls. These cells also showed an impaired cooperation between TACI and TLR9 pathways, as well as a lack of APRIL-mediated enhancement of CD40 activation in suboptimal conditions. Finally, after APRIL ligation, S231R-mutated TACI failed to colocalize with MyD88. Collectively, these results highlight the requirement of an intact MyD88-binding site in TACI to trigger CSR.Fil: Almejún, María Belén. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Laboratorio de Investigación; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cols, Montserrat. Mount Sinai School of Medicine. Department of Medicine; Estados UnidosFil: Zelazko, Marta. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Laboratorio de Investigación; ArgentinaFil: Oleastro, Matías. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Laboratorio de Investigación; ArgentinaFil: Cerutti, Andrea. Mount Sinai School of Medicine. Department of Medicine; Estados UnidosFil: Oppezzo, Pablo. Instituto Pasteur. Unidad de Proteínas Recombinantes; UruguayFil: Cunningham Rundles, Charlotte. Mount Sinai School of Medicine. Department of Medicine; Estados UnidosFil: Danielian, Silvia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Laboratorio de Investigación; ArgentinaWiley VCH Verlag2013-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/3243Almejún, María Belén; Cols, Montserrat; Zelazko, Marta; Oleastro, Matías; Cerutti, Andrea; et al.; Naturally occurring mutation affecting the MyD88-binding site of TNFRSF13B impairs triggering of class switch recombination; Wiley VCH Verlag; European Journal of Immunology; 43; 3; 3-2013; 805-8140014-2980enginfo:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1002/eji.201242945/abstract;jsessionid=4AD42FD3938BE6D63A8ACD070D492D4E.f02t01info:eu-repo/semantics/altIdentifier/doi/10.1002%2Feji.201242945info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T12:11:13Zoai:ri.conicet.gov.ar:11336/3243instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-22 12:11:13.263CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Naturally occurring mutation affecting the MyD88-binding site of TNFRSF13B impairs triggering of class switch recombination
title Naturally occurring mutation affecting the MyD88-binding site of TNFRSF13B impairs triggering of class switch recombination
spellingShingle Naturally occurring mutation affecting the MyD88-binding site of TNFRSF13B impairs triggering of class switch recombination
Almejún, María Belén
Class Switch Recombination
Myd88
Common Variable Immunodeficiency
Taci
title_short Naturally occurring mutation affecting the MyD88-binding site of TNFRSF13B impairs triggering of class switch recombination
title_full Naturally occurring mutation affecting the MyD88-binding site of TNFRSF13B impairs triggering of class switch recombination
title_fullStr Naturally occurring mutation affecting the MyD88-binding site of TNFRSF13B impairs triggering of class switch recombination
title_full_unstemmed Naturally occurring mutation affecting the MyD88-binding site of TNFRSF13B impairs triggering of class switch recombination
title_sort Naturally occurring mutation affecting the MyD88-binding site of TNFRSF13B impairs triggering of class switch recombination
dc.creator.none.fl_str_mv Almejún, María Belén
Cols, Montserrat
Zelazko, Marta
Oleastro, Matías
Cerutti, Andrea
Oppezzo, Pablo
Cunningham Rundles, Charlotte
Danielian, Silvia
author Almejún, María Belén
author_facet Almejún, María Belén
Cols, Montserrat
Zelazko, Marta
Oleastro, Matías
Cerutti, Andrea
Oppezzo, Pablo
Cunningham Rundles, Charlotte
Danielian, Silvia
author_role author
author2 Cols, Montserrat
Zelazko, Marta
Oleastro, Matías
Cerutti, Andrea
Oppezzo, Pablo
Cunningham Rundles, Charlotte
Danielian, Silvia
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Class Switch Recombination
Myd88
Common Variable Immunodeficiency
Taci
topic Class Switch Recombination
Myd88
Common Variable Immunodeficiency
Taci
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Mutations in the transmembrane activator and calcium-modulating cyclophilin ligand interactor (TACI) were previously found to be associated with hypogammaglobulinemia in humans. It has been shown that proliferation inducing ligand (APRIL) elicits class switch recombination (CSR) by inducing recruitment of MyD88 to a TACI highly conserved cytoplasmic domain (THC). We have identified a patient with hypogammaglobulinemia carrying a missense mutation (S231R) predicted to affect the THC. Aiming to evaluate the relevance of this novel mutation of TACI in CSR induction, we tested the ability of TACI, TLR9, or/and CD40 ligands to trigger CSR in naive B cells and B-cell lines carrying S231R. IgG secretion was impaired when triggered by TACI or/and TLR9 ligands on S231R-naive B cells. Likewise, these stimuli induced less expression of activation-induced cytidine deaminase, I(γ)1-C(μ), and I(γ)1-C(μ), while induction by optimal CD40 stimulation was indistinguishable from controls. These cells also showed an impaired cooperation between TACI and TLR9 pathways, as well as a lack of APRIL-mediated enhancement of CD40 activation in suboptimal conditions. Finally, after APRIL ligation, S231R-mutated TACI failed to colocalize with MyD88. Collectively, these results highlight the requirement of an intact MyD88-binding site in TACI to trigger CSR.
Fil: Almejún, María Belén. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Laboratorio de Investigación; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Cols, Montserrat. Mount Sinai School of Medicine. Department of Medicine; Estados Unidos
Fil: Zelazko, Marta. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Laboratorio de Investigación; Argentina
Fil: Oleastro, Matías. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Laboratorio de Investigación; Argentina
Fil: Cerutti, Andrea. Mount Sinai School of Medicine. Department of Medicine; Estados Unidos
Fil: Oppezzo, Pablo. Instituto Pasteur. Unidad de Proteínas Recombinantes; Uruguay
Fil: Cunningham Rundles, Charlotte. Mount Sinai School of Medicine. Department of Medicine; Estados Unidos
Fil: Danielian, Silvia. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan". Laboratorio de Investigación; Argentina
description Mutations in the transmembrane activator and calcium-modulating cyclophilin ligand interactor (TACI) were previously found to be associated with hypogammaglobulinemia in humans. It has been shown that proliferation inducing ligand (APRIL) elicits class switch recombination (CSR) by inducing recruitment of MyD88 to a TACI highly conserved cytoplasmic domain (THC). We have identified a patient with hypogammaglobulinemia carrying a missense mutation (S231R) predicted to affect the THC. Aiming to evaluate the relevance of this novel mutation of TACI in CSR induction, we tested the ability of TACI, TLR9, or/and CD40 ligands to trigger CSR in naive B cells and B-cell lines carrying S231R. IgG secretion was impaired when triggered by TACI or/and TLR9 ligands on S231R-naive B cells. Likewise, these stimuli induced less expression of activation-induced cytidine deaminase, I(γ)1-C(μ), and I(γ)1-C(μ), while induction by optimal CD40 stimulation was indistinguishable from controls. These cells also showed an impaired cooperation between TACI and TLR9 pathways, as well as a lack of APRIL-mediated enhancement of CD40 activation in suboptimal conditions. Finally, after APRIL ligation, S231R-mutated TACI failed to colocalize with MyD88. Collectively, these results highlight the requirement of an intact MyD88-binding site in TACI to trigger CSR.
publishDate 2013
dc.date.none.fl_str_mv 2013-03
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/3243
Almejún, María Belén; Cols, Montserrat; Zelazko, Marta; Oleastro, Matías; Cerutti, Andrea; et al.; Naturally occurring mutation affecting the MyD88-binding site of TNFRSF13B impairs triggering of class switch recombination; Wiley VCH Verlag; European Journal of Immunology; 43; 3; 3-2013; 805-814
0014-2980
url http://hdl.handle.net/11336/3243
identifier_str_mv Almejún, María Belén; Cols, Montserrat; Zelazko, Marta; Oleastro, Matías; Cerutti, Andrea; et al.; Naturally occurring mutation affecting the MyD88-binding site of TNFRSF13B impairs triggering of class switch recombination; Wiley VCH Verlag; European Journal of Immunology; 43; 3; 3-2013; 805-814
0014-2980
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1002/eji.201242945/abstract;jsessionid=4AD42FD3938BE6D63A8ACD070D492D4E.f02t01
info:eu-repo/semantics/altIdentifier/doi/10.1002%2Feji.201242945
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley VCH Verlag
publisher.none.fl_str_mv Wiley VCH Verlag
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 12.982451

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