Department of Microbiology and Immunology, Stanford University, Stanford, CA, USA.
Department of Physiology & Biophysics, University of California, Irvine, Irvine, CA, USA.
Nat Med. 2021 Jan;27(1):125-135. doi: 10.1038/s41591-020-01145-0. Epub 2021 Jan 11.
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.
我们对适应性免疫的了解大多来自近交系小鼠研究，而这些研究方法在人类中往往难以或不可能得到证实。此外，小鼠的疫苗反应通常很难预测对人类使用相同疫苗的反应。在这里，我们使用人扁桃体，一种易于获得的淋巴器官，开发了一种功能性器官型系统，可在体外重现生发中心的关键特征，包括产生抗原特异性抗体、体细胞高频突变和亲和力成熟、浆母细胞分化和类别转换重组。我们使用该系统来定义产生流感疫苗反应所需的基本细胞成分。我们还表明，它可用于评估两种初始抗原（狂犬病疫苗和基于腺病毒的严重急性呼吸综合征冠状病毒 2 疫苗）的体液免疫反应，并评估不同佐剂的效果。与以前相比，该系统应该能够更深入地研究适应性免疫的关键机制，并在完全人类系统中快速测试候选疫苗和佐剂。
