Evidence map›Paper›PMID 28077418›Full record

ArticleBlood2017

A novel humanized mouse model with significant improvement of class-switched, antigen-specific antibody production.

Hua Yu, Chiara Borsotti, Jean-Nicolas Schickel, Shu Zhu, Till Strowig, Elizabeth E Eynon, Davor Frleta, Cagan Gurer, Andrew J Murphy, George D Yancopoulos and 3 more

Open access · bronzeAbstract read
In one paragraph

Article in Blood, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers.

0numbers the graph read from it
0cells of the map it votes in
97citing papers in PubMed
5.0field-weighted citation impact, top 4% 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

97 citing papers in PubMed, 127 citations in OpenAlex.

  1. Article
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  9. Article
  10. Sex Differences in Lung B Cell Responses in a Murine Model of Asthma.International archives of allergy and immunology · 2026
    Article
  11. Article
  12. Humanization of CD47 enables development of functional human neutrophils via postirradiation remodeling of the bone marrow.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
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37 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 4 institutions in 2 countries.

Hua YuDepartment of Immunobiology, Yale University, New Haven, CT.ORCID 0000-0002-1691-2763
Chiara BorsottiDivision of Hematology, University Hospital Zurich, Zurich, Switzerland.
Jean-Nicolas SchickelDepartment of Immunobiology, Yale University, New Haven, CT.
Shu ZhuDepartment of Immunobiology, Yale University, New Haven, CT.
Till StrowigDepartment of Immunobiology, Yale University, New Haven, CT.
Elizabeth E EynonDepartment of Immunobiology, Yale University, New Haven, CT.
Davor FrletaRegeneron Pharmaceuticals, Inc., Tarrytown, NY; and.
Cagan GurerRegeneron Pharmaceuticals, Inc., Tarrytown, NY; and.
Andrew J MurphyRegeneron Pharmaceuticals, Inc., Tarrytown, NY; and.
George D YancopoulosRegeneron Pharmaceuticals, Inc., Tarrytown, NY; and.
Eric MeffreDepartment of Immunobiology, Yale University, New Haven, CT.
Markus G ManzDivision of Hematology, University Hospital Zurich, Zurich, Switzerland.
Richard A FlavellDepartment of Immunobiology, Yale University, New Haven, CT.ORCID 0000-0003-4461-0778
Yale University · USRegeneron (United States) · USUniversity Hospital of Zurich · CHHoward Hughes Medical Institute · US

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
Yale Pathology Tissue Services Shared ResourceP30CA016359 · NCI · YALE UNIVERSITY · PI MARCUS W BOSENBERG · 1985 to 2026
$85.0M
Regulation of IgA class switching in the intestinal mucosaP01AI061093 · NIAID · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI CASANOVA, JEAN-LAURENT · 2004 to 2021
$29.8M
Understanding Hemotopoietic Neoplasias using Humanized MiceR01CA156689 · NCI · YALE UNIVERSITY · PI DHODAPKAR, MADHAV V, FLAVELL, RICHARD A · 2010 to 2014
$5.0M
NCATS NIH HHS UL1 TR001863NCI NIH HHS P30 CA016359NCI NIH HHS R01 CA156689NIAID NIH HHS P01 AI061093
6 · The paper itself

Abstract

Humanized mice are a powerful tool for the study of human hematopoiesis and immune function in vivo. However, the existing models cannot support robust adaptive immune responses, especially the generation of class-switched, antigen-specific antibody responses. Here we describe a new mouse strain, in which human interleukin 6 (IL-6) gene encoding the cytokine that is important for B- and T-cell differentiation was knocked into its respective mouse locus. The provision of human IL-6 not only enhanced thymopoiesis and periphery T-cell engraftment, but also significantly increased class switched memory B cells and serum immunoglobulin G (IgG). In addition, immunization with ovalbumin (OVA) induced OVA-specific B cells only in human IL-6 knock-in mice. These OVA-specific antibodies displayed the highest frequency of somatic mutation, further suggesting that human IL-6 is important for efficient B-cell activation and selection. We conclude that human IL-6 knock-in mice represent a novel and improved model for human adaptive immunity without relying on complex surgery to transplant human fetal thymus and liver. These mice can therefore be used to exploit or evaluate immunization regimes that would be unethical or untenable in humans.

Indexed as

Adaptive ImmunityAntibody FormationGene Knock-In TechniquesImmunoglobulin Class SwitchingAnimalsB-LymphocytesChickensGene ExpressionHematopoietic Stem CellsHematopoietic Stem Cell TransplantationHumansImmunizationImmunoglobulin GInterleukin-6MiceOvalbuminIL6 protein, humanImmunoglobulin GInterleukin-6Ovalbumin

Identifiers

PMID28077418
PMCPMC5324713
OpenAlexW2572655490

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.