ArticleThe Journal of experimental medicine2021
Activated PI3Kδ signals compromise plasma cell survival via limiting autophagy and increasing ER stress.
Article in The Journal of experimental medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Canonical and noncanonical autophagy in immunity.Immunity · 2026Review
- Activated PIK3CD drives marginal zone B cell development from early transitional progenitors by enhancing ADAM10 expression.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- PI3Kdelta-driven expansion of regulatory B cells impairs protective immune responses to Trypanosoma congolense parasite infection.PLoS pathogens · 2025Article
- Chronic Antibody-Mediated Rejection and Plasma Cell ER Stress: Opportunities and Challenges with Calcineurin Inhibitors.International journal of molecular sciences · 2025Review
- SIV-specific neutralizing antibody induction following selection of a PI3K drive-attenuatedeLife · 2025Article
- ROCK1 promotes B cell differentiation and proteostasis under stress through the heme-regulated proteins, BACH2 and HRI.JCI insight · 2025Article
- Biallelic PI4KA Mutations Disrupt B-Cell Metabolism and Cause B-Cell Lymphopenia and Hypogammaglobulinemia.Journal of clinical immunology · 2024Article
- Activated PI3Kδ Specifically Perturbs Mouse Regulatory T Cell Homeostasis and Function Leading to Immune Dysregulation.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Activated PI3Kδ specifically perturbs mouse Treg homeostasis and function leading to immune dysregulation.bioRxiv : the preprint server for biology · 2023Article
- Human PIK3R1 mutations disrupt lymphocyte differentiation to cause activated PI3Kδ syndrome 2.The Journal of experimental medicine · 2023Article
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Authors and funding
9 authors.
Funding
Abstract
While phosphatidylinositide 3-kinase delta (PI3Kδ) plays a critical role in humoral immunity, the requirement for PI3Kδ signaling in plasma cells remains poorly understood. Here, we used a conditional mouse model of activated PI3Kδ syndrome (APDS), to interrogate the function of PI3Kδ in plasma cell biology. Mice expressing a PIK3CD gain-of-function mutation (aPIK3CD) in B cells generated increased numbers of memory B cells and mounted an enhanced secondary response but exhibited a rapid decay of antibody levels over time. Consistent with these findings, aPIK3CD expression markedly impaired plasma cell generation, and expression of aPIK3CD intrinsically in plasma cells was sufficient to diminish humoral responses. Mechanistically, aPIK3CD disrupted ER proteostasis and autophagy, which led to increased plasma cell death. Notably, this defect was driven primarily by elevated mTORC1 signaling and modulated by treatment with PI3Kδ-specific inhibitors. Our findings establish an essential role for PI3Kδ in plasma cell homeostasis and suggest that modulating PI3Kδ activity may be useful for promoting and/or thwarting specific immune responses.
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