Potentiation of noncanonical NF-κB signaling and marginal zone B cell expansion by CARD11-mediated regulation of p100 processing.

ABSTRACT: The signaling scaffold CARD11 is critical for adaptive immunity and antigen receptor signaling to canonical nuclear factor κB (NF-κB), mTOR, JNK, and AKT. Oncogenic gain-of-function (GoF) CARD11 mutants, implicated in a variety of lymphomas, bypass regulation and signal constitutively. In mice expressing the lymphoma-associated mutation CARD11 C49Y, we observe B cell expansion that is most impressive for marginal zone (MZ) B cells. CARD11^C49Y/C49Y MZ B cells exhibit enhanced cell-autonomous survivability and elevated basal levels of the precursor NF-κB subunit p100, which is inducibly processed, leading to elevated nuclear p52 levels in response to B cell activating factor (BAFF). We show that active CARD11 variants can inhibit basal NIK-induced p100 processing to p52 independen

SUBMITTER: Ghosh A 

PROVIDER: S-EPMC12818902 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature