Somatic deficiency of the human E3 ubiquitin ligase CBL in leukocytes impairs B cell but not T cell development and function
Articolo
Data di Pubblicazione:
2026
Abstract:
The E3 ubiquitin ligase Casitas B-lineage lymphoma (CBL) promotes positive selection and antigen responses in mouse T lymphocytes by ubiquitinating ZAP70. Conversely, mouse CBL and CBL-B mutually redundantly regulate SYK ubiquitination and B cell receptor signaling. Here we studied individuals with somatically homozygous CBL loss-of-function variants in leukocytes. Human CBL is largely redundant for the development and function of human T cells. Conversely, B cell development is altered at the immature stage, with a tenfold increase in transitional cells, enhanced survival of autoreactive clones and impaired tolerance manifested by autoantibody production. B cell maturation is intrinsically impaired by reduced apoptosis and dysregulated B cell receptor signaling. CBL deficiency impairs humoral immunity by limiting memory B cell formation and reducing class switching and somatic hypermutation. Consequently, antigen-specific B cell generation and adaptive immune memory are disrupted, predisposing individuals to infection. Human CBL is critical for B cell development and function but redundant for T cell biology.
Tipologia CRIS:
1.1 Articolo in rivista
Elenco autori:
Vatovec, Taja; Neehus, Anna-Lena; Jackson, Katherine J. L.; Avery, Danielle T.; Bagarić, Ivan; Erazo, Lucia; Arango-Franco, Carlos A.; Ogishi, Masato; Ahmed, Syed F.; Cederholm, Axel; Russell, Amanda J.; Della Mina, Erika; Al-Rifai, Dena; Bull, Rowena; Buetow, Lori; Sobrino, Steicy; Zhang, Allison; Wahlster, Lara; Michelet, Marine; Parvaneh, Nima; Peel, Jessica; Barzaghi, Federica; Leardini, Davide; Philippot, Quentin; Saettini, Francesco; Dutrieux, Jacques; De Muylder, Benedicte; Vendemini, Francesca; Baccelli, Francesco; Catala, Albert; Gambineri, Eleonora; Veltroni, Marinella; Pandiarajan, Vignesh; Aguilar, Yurena; Haerynck, Filomeen; Elliott, Michael; Turville, Stuart; Brillot, Fabienne; Khan, Taushif; Consonni, Filippo; Berteloot, Laureline; Sewell, William A.; Rao, Geetha; Largeaud, Laetitia; Conti, Francesca; Roullion, Cecile; Masson, Cécile; Pegoraro, Francesco; Ye, Tianyi; Joubran, Samantha; Villalpando, Emily; Bessot, Boris; Seeleuthner, Yoann; Le Voyer, Tom; Rosain, Jérémie; Li, Hailun; Janda, Zarah; Muratore, Edoardo; Soudée, Camille; Delabesse, Eric; Goulvestre, Claire; Shahrooei, Mohammad; Puel, Anne; André, Isabelle; Bole-Feysot, Christine; Abel, Laurent; Erlacher, Miriam; Béziat, Vivien; Lagresle-Peyrou, Chantal; Cheynier, Remi; Six, Emmanuelle; Marr, Nico; Pasquet, Marlène; Alsina, Laia; Goodnow, Christopher C.; Landegren, Nils; Aiuti, Alessandro; Zhang, Peng; Masetti, Riccardo; Huang, Danny T.; Ma, Cindy S.; Casanova, Jean-Laurent; Sankaran, Vijay G.; Bustamante, Jacinta; Tangye, Stuart G.; Bohlen, Jonathan
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