Modeling human adaptive immune responses with tonsil organoids.

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.

journal_name

Nat Med

journal_title

Nature medicine

authors

Wagar LE,Salahudeen A,Constantz CM,Wendel BS,Lyons MM,Mallajosyula V,Jatt LP,Adamska JZ,Blum LK,Gupta N,Jackson KJL,Yang F,Röltgen K,Roskin KM,Blaine KM,Meister KD,Ahmad IN,Cortese M,Dora EG,Tucker SN,Sperling AI

doi

10.1038/s41591-020-01145-0

subject

Has Abstract

pub_date

2021-01-01 00:00:00

pages

125-135

issue

1

eissn

1078-8956

issn

1546-170X

pii

10.1038/s41591-020-01145-0

journal_volume

27

pub_type

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