AIM2 positively regulates B cell activation and function through the SNX9-PI3K-WASP axis
Yanmei Huang1, Pengyue Gao2, Li Luo1
1Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Cell Death and Differentiation
|December 24, 2025
Summary
AIM2, an inflammasome sensor, plays a novel role in B cell function, regulating B cell receptor signaling and antibody production. Its dysregulation contributes to autoimmune diseases like Kawasaki disease.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- AIM2 inflammasome sensor is known for pyroptosis in macrophages.
- Its role in adaptive immunity, especially B cells, is largely uncharacterized.
Purpose of the Study:
- To investigate the function of AIM2 in B cells and its role in adaptive immunity.
- To elucidate the molecular mechanisms underlying AIM2's regulation of B cell receptor signaling.
Main Methods:
- AIM2 knockout mice models.
- B cell activation assays.
- Immunoprecipitation-mass spectrometry (IP-MS).
- Analysis of signaling pathways (PI3K-AKT, BTK-NFκB).
Main Results:
- AIM2 deficiency reduced B cell subsets and impaired IgG3 switching.
- AIM2 positively regulates PI3K-AKT and negatively regulates BTK-NFκB signaling.
- SNX9 is identified as a key mediator in AIM2-dependent BCR signaling and endocytosis.
- AIM2 knockout mice showed reduced BCR signaling, calcium signaling, and antibody production.
- AIM2 is overexpressed in B cells of Kawasaki disease patients.
Conclusions:
- AIM2 has a novel positive regulatory role in B cell receptor activation, endocytosis, and humoral response.
- AIM2-associated signaling pathways are critical for B cell function.
- AIM2 dysregulation contributes to autoimmune diseases.
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