Activated PI3Kδ breaches multiple B cell tolerance checkpoints and causes autoantibody production

In patients, gain-of-function (GOF) mutations in PIK3CD break tolerance, causing highly penetrant secretion of autoreactive IgM. Mouse models reveal that Pik3cd GOF subverts the response to self-antigen, preventing the induction of anergy and instead stimulating plasmablast and GC formation.

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