分泌白细胞介素-2的T辅助细胞通过对B细胞mTOR-AKT-Blimp-1轴的内在调控促进滤泡外B细胞成熟

IF 25.5 1区 医学 Q1 IMMUNOLOGY
Caterina E. Faliti, Maria Mesina, Jinyong Choi, Simon Bélanger, Monique A. Marshall, Christopher M. Tipton, Sakeenah Hicks, Prashanti Chappa, Maria A. Cardenas, Mohamed Abdel-Hakeem, Theresa C. Thinnes, Christopher Cottrell, Christopher D. Scharer, William R. Schief, David Nemazee, Matthew C. Woodruff, John M. Lindner, Ignacio Sanz, Shane Crotty
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引用次数: 0

摘要

在抗原驱动的应答过程中,B细胞可在滤泡外(EF)部位分化或启动生殖中心(GC),其过程涉及与T细胞的相互作用。在这里,我们研究了T辅助细胞(Th)在与活化B细胞发生同源相互作用时分泌的白细胞介素(IL)-2的作用。IL-2 促进了 EF 浆细胞的扩增和低变异免疫球蛋白 G (IgG) 的分泌。相反,从基因上破坏 CD4+ T 细胞的 IL-2 表达或 B 细胞的 IL-2 受体(CD25)表达,会促进 B 细胞进入 GC 并分泌高亲和力抗体。从机理上讲,IL-2诱导了早期mTOR活性、转录调节因子IRF4的表达,以及B细胞形成Blimp-1表达浆细胞所需的代谢变化。因此,T细胞通过IL-2帮助调节活化B细胞中的mTOR-AKT-Blimp-1轴,从而深入了解了决定EF与GC命运的机制,并将IL-2定位为控制浆细胞与GC B细胞承诺的早期开关。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Interleukin-2-secreting T helper cells promote extra-follicular B cell maturation via intrinsic regulation of a B cell mTOR-AKT-Blimp-1 axis

Interleukin-2-secreting T helper cells promote extra-follicular B cell maturation via intrinsic regulation of a B cell mTOR-AKT-Blimp-1 axis
During antigen-driven responses, B cells can differentiate at extra-follicular (EF) sites or initiate germinal centers (GCs) in processes that involve interactions with T cells. Here, we examined the roles of interleukin (IL)-2 secreted by T helper (Th) cells during cognate interactions with activated B cells. IL-2 boosted the expansion of EF plasma cells and the secretion of low-mutated immunoglobulin G (IgG). Conversely, genetically disrupting IL-2 expression by CD4+ T cells, or IL-2 receptor (CD25) expression by B cells, promoted B cell entry into the GC and high-affinity antibody secretion. Mechanistically, IL-2 induced early mTOR activity, expression of the transcriptional regulator IRF4, and metabolic changes in B cells required to form Blimp-1-expressing plasma cells. Thus, T cell help via IL-2 regulates an mTOR-AKT-Blimp-1 axis in activated B cells, providing insight into the mechanisms that determine EF versus GC fates and positioning IL-2 as an early switch controlling plasma cell versus GC B cell commitment.
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来源期刊
Immunity
Immunity 医学-免疫学
CiteScore
49.40
自引率
2.20%
发文量
205
审稿时长
6 months
期刊介绍: Immunity is a publication that focuses on publishing significant advancements in research related to immunology. We encourage the submission of studies that offer groundbreaking immunological discoveries, whether at the molecular, cellular, or whole organism level. Topics of interest encompass a wide range, such as cancer, infectious diseases, neuroimmunology, autoimmune diseases, allergies, mucosal immunity, metabolic diseases, and homeostasis.
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