Modeling human adaptive immune responses with tonsil organoids

An in vitro human tonsil tissue-based system captures key features of a functional germinal center and can be used to study humoral immune responses to vaccines, new antigens and adjuvants. 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.

Automated summary

By utilizing human tonsils, researchers have developed a functional organotypic system that mimics key features of germinal centers in vitro, allowing for the study of humoral immune responses. This system not only enables a deeper understanding of critical mechanisms underlying adaptive immunity, but also facilitates rapid testing of vaccine candidates and adjuvants in an entirely human system.