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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/3243
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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 Técnicas2025-09-29T10:38:58Zoai: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:34982025-09-29 10:38:59.127CONICET 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 |
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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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1844614413892452352 |
score |
13.070432 |