Inherited BCL10 deficiency impairs hematopoietic and nonhematopoietic immunity



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Torres, Juan Manuel and Martínez Barricarte, Rubén and García Gómez, Sonia and Mazariegos, Marina S and Itan, Yuval and Boisson, Bertrand and Álvarez Carbajal, Rita Lucía and Jiménez Reinoso, Anaïs and del Pino, Lucía and Rodríguez Pena, Rebeca and Ferreira Martín, Antonio and Hernández Jiménez, Enrique and Toledano, Víctor and Cubillos Zapata, Carolina and Díaz Almirón, Mariana and López Collazo, Eduardo and Unzueta Roch, José L and Sánchez Ramón, Silvia María and Regueiro González-Barros, José Ramón and López Granados, Eduardo and Casanova, Jean-Laurent and Pérez de Diego, Rebeca (2014) Inherited BCL10 deficiency impairs hematopoietic and nonhematopoietic immunity. The Journal of Clinical Investigation, 124 (12). pp. 5239-5248. ISSN 0021-9738 (print), 1558-8238 (online)

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Heterotrimers composed of B cell CLL/lymphoma 10 (BCL10), mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1), and caspase recruitment domain–containing (CARD) family adaptors play a role in NF-κB activation and have been shown to be involved in both the innate and the adaptive arms of immunity in murine models. Moreover, individuals with inherited defects of MALT1, CARD9, and CARD11 present with immunological and clinical phenotypes. Here, we characterized a case of autosomal-recessive, complete BCL10 deficiency in a child with a broad immunodeficiency, including defects of both hematopoietic and nonhematopoietic immunity. The patient died at 3 years of age and was homozygous for a loss-of-expression, loss-of function BCL10 mutation. The effect of BCL10 deficiency was dependent on the signaling pathway, and, for some pathways, the cell type affected. Despite the noted similarities to BCL10 deficiency in mice, including a deficient adaptive immune response, human BCL10 deficiency in this patient resulted in a number of specific features within cell populations. Treatment of the patient’s myeloid cells with a variety of pathogen-associated molecular pattern molecules (PAMPs) elicited a normal response; however, NF-κB–mediated fibroblast functions were dramatically impaired. The results of this study indicate that inherited BCL10 deficiency should be considered in patients with combined immunodeficiency with B cell, T cell, and fibroblast defects.

Item Type:Article
Subjects:Medical sciences > Medicine > Immunology
ID Code:69220
Deposited On:16 Dec 2021 09:59
Last Modified:16 Dec 2021 09:59

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