Evidence map›Paper›PMID 22592523›Full record

ArticleGenes and immunity2012

Human B-cell ontogeny in humanized NOD/SCID γc(null) mice generates a diverse yet auto/poly- and HIV-1-reactive antibody repertoire.

H Chang, S Biswas, A S Tallarico, P T N Sarkis, S Geng, M M Panditrao, Q Zhu, W A Marasco

Abstract read
In one paragraph

Article in Genes and immunity, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
–field-weighted citation impact
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

22 citing papers in PubMed.

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  8. Message from the new Editors-in-Chief.Genes and immunity · 2019
    Article
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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

8 authors.

H ChangDepartment of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
S Biswas
A S Tallarico
P T N Sarkis
S Geng
M M Panditrao
Q Zhu
W A Marasco

Funding

Immunotherapeutics for Treatment of Flavivirus InfectionU01AI070343 · NIAID · YALE UNIVERSITY · PI FIKRIG, EROL · 2006 to 2010
$6.6M
Interactions Between Anaplasma Phagocytophilum and Ixodes ScapularisR01AI041440 · NIAID · YALE UNIVERSITY · PI FIKRIG, EROL · 1998 to 2014
$5.0M
Study of broadly neutralizing antibody generation to HIV gp140 in humanized miceR21AI091557 · NIAID · DANA-FARBER CANCER INST · PI MARASCO, WAYNE A. · 2010 to 2011
$432k
NIAID NIH HHS R01 AI041440NIAID NIH HHS R21 AI091557NIAID NIH HHS U01 AI0070343NIAID NIH HHS U01 AI070343
6 · The paper itself

Abstract

Characterization of the human antibody (Ab) repertoire in mouse models of the human immune system is essential to establish their relevance in translational studies. Single human B cells were sorted from bone marrow and periphery of humanized NOD/SCID γc(null) (hNSG) mice at 8-10 months post engraftment with human cord blood-derived CD34(+) stem cells. Human IG variable heavy (V(H)) and kappa (V(κ)) genes were amplified, cognate V(H)-V(κ) gene-pairs assembled as single-chain variable fragment-Fc Abs (scFvFcs) and functional studies were performed. Although overall distribution of V(H) genes approximated the normal human Ab repertoire, analysis of the V(H)-third complementarity-determining regions in the mature B-cell subset demonstrated an increase in length and positive charges, suggesting autoimmune characteristics. Additionally, >70% of V(κ) sequences utilized V(κ)4-1, a germline gene associated with autoimmunity. The mature B-cell subset-derived scFvFcs displayed the highest frequency of autoreactivity and polyspecificity, suggesting defects in checkpoint control mechanisms. Furthermore, these scFvFcs demonstrated binding to recombinant HIV envelope corroborating previous observations of poly/autoreactivity in anti-HIVgp140 Abs. These data lend support to the hypothesis that anti-HIV broadly neutralizing antibodies may be derived from auto/polyspecific Abs that escaped immune elimination and that the hNSG mouse could provide a new experimental platform for studying the origin of anti-HIV-neutralizing Ab responses.

Indexed as

AnimalsAutoantibodiesB-Lymphocytesenv Gene Products, Human Immunodeficiency VirusFemaleGene Rearrangement, B-Lymphocyte, Heavy ChainHIV-1HIV AntibodiesHumansImmunoglobulin Heavy ChainsMaleMiceMice, Inbred NODMice, SCIDProtein BindingSomatic Hypermutation, ImmunoglobulinAutoantibodiesenv Gene Products, Human Immunodeficiency Virusgp140 envelope protein, Human immunodeficiency virus 1HIV AntibodiesImmunoglobulin Heavy Chains

Identifiers

PMID22592523
PMCPMC3411862

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Registered trials

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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.