Naturally occurring mutation affecting the MyD88-binding site of TNFRSF13B impairs triggering of class switch recombination
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 recruitm...
| Autores: | ; ; ; ; ; ; ; |
|---|---|
| Tipo de documento: | Artículo |
| Estado: | Published version |
| Fecha de publicación: | 2013 |
| País: | Argentina |
| Institución: | Consejo Nacional de Investigaciones Científicas y Técnicas |
| Repositorio: | CONICET Digital (CONICET) |
| Lenguaje: | Inglés |
| OAI Identifier: | oai:ri.conicet.gov.ar:11336/3243 |
| Acceso en línea: | http://hdl.handle.net/11336/3243 |
| Nivel de acceso: | Acceso abierto |
| Palabra clave: | Class Switch Recombination Myd88 Common Variable Immunodeficiency Taci https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 |
| _version_ | 1878403038455005184 |
|---|---|
| author | Almejún, María Belén |
| 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 |
| author_browse | Almejún, María Belén Cerutti, Andrea Cols, Montserrat Cunningham Rundles, Charlotte Danielian, Silvia Oleastro, Matías Oppezzo, Pablo Zelazko, Marta |
| author_facet | Almejún, María Belén Cols, Montserrat Zelazko, Marta Oleastro, Matías Cerutti, Andrea Oppezzo, Pablo Cunningham Rundles, Charlotte Danielian, Silvia |
| author_role | author |
| collection | CONICET Digital (CONICET) |
| 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. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | AR_31acf4eb3fc08d7cd8840e2f8ef409c5 |
| 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 |
| institution | Consejo Nacional de Investigaciones Científicas y Técnicas |
| instname_str | Consejo Nacional de Investigaciones Científicas y Técnicas |
| language | eng |
| network_acronym_str | AR |
| network_name_str | Argentina |
| oai_identifier_str | oai:ri.conicet.gov.ar:11336/3243 |
| publishDate | 2013 |
| publishDateSort | 2013 |
| publisher | Wiley VCH Verlag |
| publisherStr | Wiley VCH Verlag |
| reponame_str | CONICET Digital (CONICET) |
| spelling | Naturally occurring mutation affecting the MyD88-binding site of TNFRSF13B impairs triggering of class switch recombination Almejún, María Belén Cols, Montserrat Zelazko, Marta Oleastro, Matías Cerutti, Andrea Oppezzo, Pablo Cunningham Rundles, Charlotte Danielian, Silvia Class Switch Recombination Myd88 Common Variable Immunodeficiency Taci https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 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 Wiley VCH Verlag 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 |
| 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 https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 |
| status_str | publishedVersion |
| title | 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_short | 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 |
| topic | Class Switch Recombination Myd88 Common Variable Immunodeficiency Taci https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 |
| topic_facet | Class Switch Recombination Myd88 Common Variable Immunodeficiency Taci https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 |
| url | http://hdl.handle.net/11336/3243 |