Evidence map›Paper›PMID 33432170›Full record

ArticleNature medicine2021

Modeling human adaptive immune responses with tonsil organoids.

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 and 20 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 221 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
221citing papers in PubMed, 1 pooled it
22.2field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

221 citing papers in PubMed, 1 synthesis or guideline pooled it, 294 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Simulated microgravity induces aging phenotypes in human organoids.bioRxiv : the preprint server for biology · 2026
    Article
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  6. Review
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  8. Article
  9. A tonsil organoid model reveals Epstein-Barr virus-infected germinal center B cell states during primary infection.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
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  12. Review
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  18. iScience · 2026
    Article
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  20. Article

161 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

30 authors at 9 institutions in 2 countries.

Lisa E WagarDepartment of Microbiology and Immunology, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0001-5980-3586
Ameen SalahudeenDepartment of Medicine, Division of Hematology, Stanford University School of Medicine, Stanford, CA, USA.
Christian M ConstantzInstitute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA.
Ben S WendelDepartment of Microbiology and Immunology, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0001-6896-3354
Michael M LyonsDepartment of Microbiology and Immunology, Stanford University, Stanford, CA, USA.
Vamsee MallajosyulaInstitute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA.
Lauren P JattInstitute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0001-7034-9046
Julia Z AdamskaDepartment of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA, USA.
Lisa K BlumDepartment of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-7921-8939
Neha GuptaInstitute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA.
Katherine J L JacksonDepartment of Pathology, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-9952-7069
Fan YangDepartment of Pathology, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0003-4821-6583
Katharina RöltgenDepartment of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
Krishna M RoskinDepartment of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
Kelly M BlaineDepartment of Medicine, University of Chicago, Chicago, IL, USA.
Kara D MeisterDepartment of Otolaryngology-Head & Neck Surgery, Stanford University School of Medicine, Stanford, CA, USA.
Iram N AhmadDepartment of Otolaryngology-Head & Neck Surgery, Stanford University School of Medicine, Stanford, CA, USA.
Mario CorteseVaxart, South San Francisco, CA, USA.
Emery G DoraVaxart, South San Francisco, CA, USA.
Sean N TuckerVaxart, South San Francisco, CA, USA.
Anne I SperlingDepartment of Medicine, University of Chicago, Chicago, IL, USA.
Aarti JainVaccine Research and Development Center, Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA, USA.
D Huw DaviesVaccine Research and Development Center, Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA, USA.
Philip L FelgnerVaccine Research and Development Center, Department of Physiology and Biophysics, University of California, Irvine, Irvine, CA, USA.
Gregory B HammerDepartments of Pediatrics and Anesthesiology, Perioperative and Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Peter S KimStanford ChEM-H, Department of Biochemistry and Chan Zuckerberg Biohub, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0001-6503-4541
William H RobinsonDepartment of Medicine, Division of Immunology and Rheumatology, Stanford University School of Medicine, Stanford, CA, USA.
Scott D BoydDepartment of Pathology, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0003-0963-044X
Calvin J KuoDepartment of Medicine, Division of Hematology, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-7427-5985
Mark M DavisDepartment of Microbiology and Immunology, Stanford University, Stanford, CA, USA. mmdavis@stanford.edu.ORCID http://orcid.org/0000-0001-6868-657X
Stanford University · USUniversity of California, Irvine · USVA Palo Alto Health Care System · USVaxart (United States) · USUniversity of Chicago · USChan Zuckerberg Initiative (United States) · USHoward Hughes Medical Institute · USLucile Packard Children's Hospital · USUniversity of Illinois Chicago · US

Funding

Using a tonsil organoid system to probe conditions for the induction of protective antibody and T cell responses to influenza.U19AI057229 · NIAID · STANFORD UNIVERSITY · PI Mark Morris Davis · 2003 to 2026
$88.5M
Stanford/UNC Biomimetic U19 Research CenterU19AI116484 · NIAID · STANFORD UNIVERSITY · PI AMIEVA, MANUEL R, KUO, CALVIN J · 2015 to 2025
$13.5M
UCSF Project 1U54CA224081 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Collin M Blakely · 2017 to 2026
$12.9M
Regulation of actively proliferating and quiescent intestinal stem cellsU01DK085527 · NIDDK · STANFORD UNIVERSITY · PI KUO, CALVIN J · 2009 to 2023
$6.9M
Intestinal Stem Cell Consortium Coordinating CenterU01DK085532 · NIDDK · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI NILAND, JOYCE CAROL · 2009 to 2018
$6.5M
Organoid-based Discovery of Oncogenic Drivers and Treatment Resistance MechanismsU01CA217851 · NCI · STANFORD UNIVERSITY · PI CURTIS, CHRISTINA N, JI, HANLEE P · 2017 to 2021
$4.7M
Effects of aging on primary and secondary vaccine responses in a 15-year longitudinal cohortR01AI130398 · NIAID · STANFORD UNIVERSITY · PI BOYD, SCOTT DEXTER · 2017 to 2021
$4.0M
Limited Competition for the Continuation of the Intestinal Stem Cell Consortium Coordinating CenterU24DK085532 · NIDDK · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · PI NILAND, JOYCE CAROL · 2019 to 2023
$2.3M
Storage and recall of human B cell memory of influenza over tissues and timeR01AI127877 · NIAID · STANFORD UNIVERSITY · PI BOYD, SCOTT DEXTER · 2017 to 2021
$2.0M
Modeling Oral Cancer in Primary Organoid CultureK08DE027730 · NIDCR · UNIVERSITY OF ILLINOIS AT CHICAGO · PI SALAHUDEEN, AMEEN A. · 2018 to 2022
$708k
Four Laser, 18 Color Cell Sorter in the SSFFS10RR025518 · NCRR · STANFORD UNIVERSITY · PI HERZENBERG, LEONARD A · 2009 to 2009
$500k
BD Canto II RUO CytometerS10RR027431 · NCRR · STANFORD UNIVERSITY · PI NOLAN, GARRY P · 2010 to 2010
$236k
NCI NIH HHS U01 CA217851NCI NIH HHS U54 CA224081NCRR NIH HHS S10 RR025518NCRR NIH HHS S10 RR027431NIAID NIH HHS R01 AI127877NIAID NIH HHS R01 AI130398NIAID NIH HHS U19 AI057229NIAID NIH HHS U19 AI116484NIDCR NIH HHS K08 DE027730NIDDK NIH HHS U01 DK085527NIDDK NIH HHS U01 DK085532NIDDK NIH HHS U24 DK085532
6 · The paper itself

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.

Indexed as

Adjuvants, ImmunologicB-LymphocytesCOVID-19 VaccinesGerminal CenterHemagglutinin Glycoproteins, Influenza VirusHumansInfluenza VaccinesIn Vitro TechniquesLymphoid TissueMeasles-Mumps-Rubella VaccineOrganoidsPalatine TonsilRabies VaccinesT-LymphocytesAdjuvants, ImmunologicCOVID-19 VaccinesH1N1 virus hemagglutininHemagglutinin Glycoproteins, Influenza VirusInfluenza VaccinesMeasles-Mumps-Rubella VaccineRabies Vaccines

Identifiers

PMID33432170
PMCPMC7891554
OpenAlexW3120919885

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.