清华大学祁海课题组提出了白细胞介素-9-ZBTB18轴促进记忆B细胞生发中心的发育。2025年3月18日出版的《免疫学》杂志发表了这项成果。

研究组研究了诱导记忆程序的机制，重点关注白细胞介素(IL)-9，考虑到它对正常回忆抗体反应的重要性。通过过继转移和辐射嵌合体模型，该研究团队发现T细胞来源的IL-9是MBC发育和功能所必需的。相比之下，缺乏IL-9的B细胞产生功能正常的MBCs，支持抗体正常召回。IL-9诱导GC记忆前体细胞和MBCs中转录抑制因子ZBTB18的表达。ZBTB18对于初始B细胞的激活和GC的形成是必不可少的，但对于GC衍生的MBCs的发展是必需的。ZBTB18直接抑制细胞周期蛋白和细胞周期蛋白依赖性激酶、促凋亡基因Bid和Casp3以及气相色谱保留因子S1pr2的表达。缺乏il -9介导的指令或ZBTB18的内在编程会损害gc源性MBC的发育和抗体召回。因此，IL-9-ZBTB18轴指导GCs功能性B细胞记忆的发展。

据介绍，记忆B细胞（MBC）从生发中心（GCs）发育而来，在细胞周期、定位和存活方面发生了深刻的变化。

附：英文原文

Title: An interleukin-9-ZBTB18 axis promotes germinal center development of memory B cells

Author: Xiaocui Luo, Xiaoxiao Hou, Yifeng Wang, Ye Li, Shangcheng Yu, Hai Qi

Issue&Volume: 2025-03-18

Abstract: Memory B cell (MBC) development from germinal centers (GCs) entails profound changes in cell cycling, localization, and survival. Here, we examined the mechanisms that induce the memory program, focusing on interleukin (IL)-9, given its importance for normal recall antibody responses. Using adoptive transfer and radiation chimera models, we found that T cell-derived IL-9 was required for MBC development and function. By contrast, B cells deficient in IL-9 generated functionally normal MBCs that support antibody recall normally. IL-9 induced expression of the transcriptional repressor ZBTB18 in GC memory precursor cells and MBCs. ZBTB18 was dispensable for naive B cell activation and GC formation but required for the development of GC-derived MBCs. ZBTB18 directly repressed the expression of a suite of genes encoding cyclin and cyclin-dependent kinases, pro-apoptotic genes Bid and Casp3, and the GC-retaining factor S1pr2. Lack of IL-9-mediated instruction or intrinsic programming by ZBTB18 impaired GC-derived MBC development and antibody recall. Thus, an IL-9-ZBTB18 axis instructs the development of functional B cell memory from GCs.

DOI: 10.1016/j.immuni.2025.02.021

Source: https://www.cell.com/immunity/abstract/S1074-7613(25)00088-3