Research ArticleIMMUNODEFICIENCIES

Pathogenic CARD11 mutations affect B cell development and differentiation through a noncanonical pathway

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Science Immunology  29 Nov 2019:
Vol. 4, Issue 41, eaaw5618
DOI: 10.1126/sciimmunol.aaw5618

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Calling CARD

CARD11 is a critical player in adaptive immunity through its role in intracellular NF-κB signaling upon antigen detection by T or B cells. CARD11 mutations are associated with different immunodeficiencies that are linked to abnormal NF-κB activation, and now Wei et al. have characterized other CARD11 mutations that affect the AKT-FOXO1 signal axis. Using three different mouse models that mimic different CARD11-associated pathologies, they showed that CARD11 can act as a negative regulator of the AKT-FOXO1 signaling axis in B cells that is independent of NF-κB. This study reveals a noncanonical role for CARD11 that influences B cell development and differentiation and provides insight into immunodeficiencies like BENTA disease.

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