eIF3e-mediated translational checkpoint maintains immune tolerance and prevents lymphoid malignancy
Year: 2026
Type: article
Abstract: Translational control is essential for immune function, but its roles in immune tolerance and lymphomagenesis remain poorly defined. Here, we show that Cγ1Cre-mediated deletion of Eif3e, which encodes a subunit of the eIF3 translation initiation complex, in B cells causes lymphoproliferation, malignant transformation of Eif3e-sufficient bystander lymphocytes, and premature death. Eif3e-deficient B cells upregulate the costimulatory molecule CD80, promoting CD4+ T cell activation and differentiation into IL-4-producing TFH-like cells. These cells, in turn, activate bystander B cells, increase MHC class II expression, and establish a feedforward loop of Eif3e deletion and lymphocyte activation. Despite their hyperactivated state, Eif3e-deficient B cells exhibit impaired proliferation, reduced survival, and defective differentiation. This self-amplifying circuit of aberrant B and T cell activation ultimately drives malignant transformation of Eif3e-sufficient lymphocytes. Our findings uncover an eIF3e-dependent translational checkpoint that preserves immune homeostasis and restrains lymphomagenesis.
DOI: 10.1084/jem.20251968
Authors: Lianghua Lin, Pengda Chen, Jiazhen Wang, Chao Huang, Xinyong Lin, Chenfeng Liu, Kunyu Liao, Jianfeng Wu, Amy Chadburn, Yunjie Zhang, Huilin Song, Chenxi Wang, Zhichen Wan, Jiayi Zhao, Guangyi Cao, Xinming Wang, Liang Yang, Nan Yao, Yazhen Hong, Zhengtao Xiao, Dieter A. Wolf, Wen-Hsien Liu, Changchun Xiao
Language: English
Topic: T-cell and B-cell Immunology
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: hybrid
OpenAlex ID: W7163416699