美国斯坦福大学Mark M. Davis研究小组用利用扁桃体类器官模拟出人类适应性免疫反应。2021年1月11日，国际知名学术期刊《自然—医学》在线发表了这一成果。

通过使用人类扁桃体（易于获得的淋巴器官），研究人员开发了功能性器官型系统，该模型概括了体外关键的生发中心特征，包括抗原特异性抗体的产生、体细胞超突变和亲和力成熟、成浆细胞分化和类别转换重组。研究人员使用该系统来定义了产生流感疫苗反应所必需的细胞成分。

结果表明，它可用于评估对两种活化抗原、狂犬病疫苗和基于腺病毒的SARS-Cov-2疫苗的体液免疫反应，并评估不同佐剂的作用。该系统可用于研究适应性免疫基础的关键机制，并且可以在整个人类系统中快速测试候选疫苗和佐剂。

据介绍，人们对适应性免疫的了解大部分来自近交小鼠研究，这些使用的方法通常难以或无法在人类中证实。另外，小鼠中的疫苗反应通常不能很好地预测人类对相同疫苗的反应。

附：英文原文

Title: Modeling human adaptive immune responses with tonsil organoids

Author: Lisa E. Wagar, Ameen Salahudeen, Christian M. Constantz, Ben S. Wendel, Michael M. Lyons, Vamsee Mallajosyula, Lauren P. Jatt, Julia Z. Adamska, Lisa K. Blum, Neha Gupta, Katherine J. L. Jackson, Fan Yang, Katharina Rltgen, Krishna M. Roskin, Kelly M. Blaine, Kara D. Meister, Iram N. Ahmad, Mario Cortese, Emery G. Dora, Sean N. Tucker, Anne I. Sperling, Aarti Jain, D. Huw Davies, Philip L. Felgner, Gregory B. Hammer, Peter S. Kim, William H. Robinson, Scott D. Boyd, Calvin J. Kuo, Mark M. Davis

Issue&Volume: 2021-01-11

Abstract: Most of what we know about adaptive immunity has come from inbred mouse studies, using methods that are often difficult or impossible to confirm in humans. In addition, vaccine responses in mice are often poorly predictive of responses to those same vaccines in humans. Here we use human tonsils, readily available lymphoid organs, to develop a functional organotypic system that recapitulates key germinal center features in vitro, including the production of antigen-specific antibodies, somatic hypermutation and affinity maturation, plasmablast differentiation and class-switch recombination. We use this system to define the essential cellular components necessary to produce an influenza vaccine response. We also show that it can be used to evaluate humoral immune responses to two priming antigens, rabies vaccine and an adenovirus-based severe acute respiratory syndrome coronavirus 2 vaccine, and to assess the effects of different adjuvants. This system should prove useful for studying critical mechanisms underlying adaptive immunity in much greater depth than previously possible and to rapidly test vaccine candidates and adjuvants in an entirely human system. 

DOI: 10.1038/s41591-020-01145-0

Source: https://www.nature.com/articles/s41591-020-01145-0