Complement-regulated homeostatic proliferation controls memory B cell longevity and repertoire composition.

IF 10.6 1区医学 Q1 IMMUNOLOGY

Journal of Experimental Medicine Pub Date : 2026-07-06 Epub Date: 2026-05-08 DOI:10.1084/jem.20251048

Evan W Cody, Mehek Ningoo, Isha Monga, Alexander M Tsankov, Hiromi Muramatsu, Norbert Pardi, Miguel Fribourg, Peter S Heeger, David Dominguez-Sola

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引用次数: 0

Abstract

Memory B cell (Bmem) survival is essential for guarding against reinfection, yet processes ensuring their longevity remain unclear. As decay-accelerating factor (DAF, CD55), a negative regulator of complement activation, is requisitely downregulated on germinal center B cells and is reexpressed on Bmem, we investigated the effects of deleting DAF on murine (B1-8hi) Bmem in competitive settings. Kinetic analysis showed a progressive reduction in DAF-/- Bmem numbers over 6 wk, without affecting Bmem production, pool size, or their ability to respond to rechallenge. Following transfer into unimmunized hosts, wild-type Bmem proliferated to maintain stable Bmem pool sizes, outcompeting DAF-/- Bmem, reflecting homeostatic proliferation. Reduced proliferation and increased cell death in DAF-/- Bmem associated with transcriptional differences in metabolism and migration pathways. Wild-type Bmem proliferation increased in C3-/- hosts, and vaccination with a heterologous antigen, which induces local complement activation, locally inhibited bystander B1-8hi Bmem proliferation. Thus, complement-dependent regulation of Bmem homeostatic proliferation influences Bmem longevity and repertoire composition in mice.

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补体调节的稳态增殖控制记忆B细胞寿命和曲目组成。

记忆B细胞（Memory B cell, Bmem）的存活对于防止再次感染至关重要，但确保其寿命的过程尚不清楚。作为补体激活的负调节因子，衰亡加速因子（DAF, CD55）在生发中心B细胞上必然下调，并在Bmem上重新表达，我们研究了在竞争环境下删除DAF对小鼠（B1-8hi） Bmem的影响。动力学分析显示，在6周内，DAF-/- Bmem数量逐渐减少，但不影响Bmem的产量、池大小或它们对再挑战的反应能力。在转移到未免疫的宿主后，野生型Bmem增殖以保持稳定的Bmem池大小，优于DAF-/- Bmem，反映了稳态增殖。DAF-/- Bmem的增殖减少和细胞死亡增加与代谢和迁移途径的转录差异有关。野生型Bmem在C3-/-宿主中增殖增加，接种诱导局部补体活化的异源抗原局部抑制旁观者B1-8hi Bmem增殖。因此，补体依赖性调节Bmem稳态增殖影响小鼠Bmem寿命和库组成。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Experimental Medicine 医学-免疫学

CiteScore

26.60

自引率

1.30%

发文量

189

审稿时长

3-8 weeks

期刊介绍： Since its establishment in 1896, the Journal of Experimental Medicine (JEM) has steadfastly pursued the publication of enduring and exceptional studies in medical biology. In an era where numerous publishing groups are introducing specialized journals, we recognize the importance of offering a distinguished platform for studies that seamlessly integrate various disciplines within the pathogenesis field. Our unique editorial system, driven by a commitment to exceptional author service, involves two collaborative groups of editors: professional editors with robust scientific backgrounds and full-time practicing scientists. Each paper undergoes evaluation by at least one editor from both groups before external review. Weekly editorial meetings facilitate comprehensive discussions on papers, incorporating external referee comments, and ensure swift decisions without unnecessary demands for extensive revisions. Encompassing human studies and diverse in vivo experimental models of human disease, our focus within medical biology spans genetics, inflammation, immunity, infectious disease, cancer, vascular biology, metabolic disorders, neuroscience, and stem cell biology. We eagerly welcome reports ranging from atomic-level analyses to clinical interventions that unveil new mechanistic insights.