美国拉霍亚免疫学研究所Shane Crotty研究组发现，分泌白细胞介素-2的T辅助细胞通过内在调控B细胞的mTOR-AKT-Blimp-1轴，促进外滤泡B细胞的成熟。这一研究成果于2024年11月28日在线发表在国际学术期刊《免疫》上。

研究人员表示，在抗原驱动的免疫反应中，B细胞可以在外滤泡（EF）部位分化，或在生发中心（GC）中启动，这些过程涉及与T细胞的相互作用。

研究人员揭示了T辅助（Th）细胞分泌的白细胞介素-2（IL-2），在与激活B细胞的特异性相互作用中的作用。IL-2促进了外滤泡浆细胞的扩展，以及低突变免疫球蛋白G（IgG）的分泌。

相反，基因上干扰CD4⁺ T细胞的IL-2表达或B细胞的IL-2受体（CD25）表达，则促进了B细胞进入GC并分泌高亲和力抗体。

在机制上，IL-2通过诱导早期的mTOR活性、转录调控因子IRF4的表达以及B细胞在形成Blimp-1表达浆细胞所需的代谢变化来发挥作用。

因此，T细胞通过IL-2提供的帮助调控了激活B细胞中的mTOR-AKT-Blimp-1轴，为揭示决定外滤泡与GC命运的机制提供了新的见解，并将IL-2定位为控制浆细胞与GC B细胞确立的早期开关。

附：英文原文

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

Author: 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

Issue&Volume: 2024-11-28

Abstract: 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.

DOI: 10.1016/j.immuni.2024.11.006

Source: https://www.cell.com/immunity/abstract/S1074-7613(24)00521-1