The B cell receptor-mTOR signaling axis restricts the accumulation of lung tissue-resident memory B cells after influenza infection.

IF 16.4 1区医学 Q1 IMMUNOLOGY

Science Immunology Pub Date : 2026-03-20 DOI:10.1126/sciimmunol.adw1664

Kumari Anupam,Komal Patel,Pradhnesh Andhare,Brittany Henry,Christopher H Hanson,Lizzette Pérez-Pérez,Peggy L Kendall,Brian J Laidlaw

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Abstract

Lung tissue-resident memory B (BRM) cells are important in establishing protective immunity against respiratory pathogens. However, the pathways regulating the accumulation of lung BRM cells are poorly understood. Here, we show that the transcription factors NFATC1 (nuclear factor of activated T cells 1) and EGR2 (early growth response 2) repress lung BRM cell accumulation after influenza infection, whereas IKZF1 (IKAROS family zinc finger 1) enhances it. IKZF1 restrains B cell receptor (BCR) and mTOR (mechanistic target of rapamycin) signaling and is highly expressed in lung BRM cells during their development. Lung BRM cells display reduced expression of genes associated with BCR and mTOR signaling pathways. Overexpression of a degradation-resistant form of SYK downstream of the BCR restricted lung BRM cell accumulation. Conversely, inhibition of mTOR using rapamycin reduced NFATC1 and EGR2 expression and promoted lung BRM cell accumulation. These findings establish how the BCR-mTOR signaling axis regulates mucosal B cell responses after influenza infection.

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B细胞受体- mtor信号轴限制流感感染后肺组织驻留记忆B细胞的积累。

肺组织驻留记忆B （BRM）细胞在建立针对呼吸道病原体的保护性免疫中起重要作用。然而，调控肺BRM细胞积聚的途径尚不清楚。在这里，我们发现转录因子NFATC1（活化T细胞的核因子1）和EGR2（早期生长反应2）抑制流感感染后肺BRM细胞的积累，而IKZF1 （IKAROS家族锌指1）则增强这种积累。IKZF1抑制B细胞受体（BCR）和mTOR（雷帕霉素的机制靶点）信号，并在肺BRM细胞发育过程中高度表达。肺BRM细胞显示与BCR和mTOR信号通路相关的基因表达降低。BCR下游抗降解形式的SYK的过度表达限制了肺BRM细胞的积累。相反，使用雷帕霉素抑制mTOR降低了NFATC1和EGR2的表达，促进了肺BRM细胞的积累。这些发现确定了BCR-mTOR信号轴如何调节流感感染后粘膜B细胞的反应。

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来源期刊

Science Immunology Immunology and Microbiology-Immunology

CiteScore

32.90

自引率

2.00%

发文量

183

期刊介绍： Science Immunology is a peer-reviewed journal that publishes original research articles in the field of immunology. The journal encourages the submission of research findings from all areas of immunology, including studies on innate and adaptive immunity, immune cell development and differentiation, immunogenomics, systems immunology, structural immunology, antigen presentation, immunometabolism, and mucosal immunology. Additionally, the journal covers research on immune contributions to health and disease, such as host defense, inflammation, cancer immunology, autoimmunity, allergy, transplantation, and immunodeficiency. Science Immunology maintains the same high-quality standard as other journals in the Science family and aims to facilitate understanding of the immune system by showcasing innovative advances in immunology research from all organisms and model systems, including humans.