Open Access 10-04-2025 | Diffuse Large B-Cell Lymphoma | Research

Role of IRF4 in mediating plasmablast differentiation in diffuse large B-cell lymphomas via mTORC1 pathway

Authors: Jingjing Gao, Chuntuan Li, Xingzhi Lin, Yanling Zhuang, Mingquan Wang, Hongjun Lin, Xiongpeng Zhu

Abstract

Autoimmune haemolytic anaemia (AIHA) is common secondary to diffuse large B-cell lymphoma (DLBCL). However, there are no reports on tumour B-cells differentiating into plasmablasts in DLBCL secondary AIHA. To state impact of the interferon regulatory factor 4 (IRF4) on DLBCL and explore the mechanism of IRF4 on plasmablast differentiation.We analysed the expression of immunity-related genes from the Gene Expression Omnibus and correlated predictors from clinical and laboratory data using R package and various statistical tools. Western blotting (WB) was used to detect protein levels in DLBCL cell lines of different subtypes to investigate the plasmablast and activation of mTORC1. To furtherly validate mTOR regulation of plasmablast differentiation, mTOR-activated and -inhibited cell models were constructed by CCK8 and flow cytometry (FCM) was used to assess the proportion of CD38 positive cells. We found that IRF4 was highly expressed in activated B-cell-like (ABC) DLBCL vs. germinal centre B-cell-like (GCB) DLBCL. Positive MUM-1and low haemoglobin values were corrected to non-CGB patients. Plasmablast indictors (BLIMP-1, ARF4, IRE1α, and IRF4) and mTORC1 pathway indictors (mTOR, p70S6K and phosphorylated-p70S6K) were different level in ABC cell lines. After successfully constructing cell models, the proportion of CD38⁺ cells changed in mTOR-activated and -inhibited ABC-DLBCL cell models. We first pointed out that the role of the IRF4 invovling in DLBCL cell plasmablast differentiation via mTORC1 pathway. These findings could be extended to provide experimental evidence for novel treatments of secondary AIHA in ABC-DLBCL.

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Title: Role of IRF4 in mediating plasmablast differentiation in diffuse large B-cell lymphomas via mTORC1 pathway
Authors: Jingjing Gao
Chuntuan Li
Xingzhi Lin
Yanling Zhuang
Mingquan Wang
Hongjun Lin
Xiongpeng Zhu
Publication date: 10-04-2025
Publisher: Springer Berlin Heidelberg
Keywords: Diffuse Large B-Cell Lymphoma
Diffuse Large B-Cell Lymphoma
Autoimmune Hemolytic Anemia
Published in: Annals of Hematology
Print ISSN: 0939-5555
Electronic ISSN: 1432-0584
DOI: https://doi.org/10.1007/s00277-025-06273-6

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Role of IRF4 in mediating plasmablast differentiation in diffuse large B-cell lymphomas via mTORC1 pathway

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