Evidence map›Paper›PMID 38381113›Full record

ArticleCardiovascular research2024

Marginal zone B cells produce 'natural' atheroprotective IgM antibodies in a T cell-dependent manner.

James Harrison, Stephen A Newland, Wei Jiang, Despoina Giakomidi, Xiaohui Zhao, Marc Clement, Leanne Masters, Andrej Corovic, Xian Zhang, Fabrizio Drago and 13 more

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

Article in Cardiovascular research, 2024. 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
5.5field-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

22 citing papers in PubMed, 23 citations in OpenAlex.

  1. Nanomaterials-Based Immunotherapy for Atherosclerosis.Small (Weinheim an der Bergstrasse, Germany) · 2026
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  12. Targeted drug delivery systems for atherosclerosis.Journal of nanobiotechnology · 2025
    Review
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  15. Tipping the Scale: Atheroprotective IgM-Producing B Cells in Atherosclerosis.Arteriosclerosis, thrombosis, and vascular biology · 2024
    Review
  16. Review
  17. T-Cell/B-Cell Interactions in Atherosclerosis.Arteriosclerosis, thrombosis, and vascular biology · 2024
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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

23 authors at 5 institutions in 4 countries.

James HarrisonDepartment of Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.
Stephen A NewlandDepartment of Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.
Wei JiangDepartment of Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.
Despoina GiakomidiDepartment of Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.
Xiaohui ZhaoDepartment of Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.
Marc ClementDepartment of Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.
Leanne MastersDepartment of Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.
Andrej CorovicDepartment of Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.
Xian ZhangDepartment of Medicine, Brigham and Woman's Hospital, Harvard Medical School, Boston, MA, USA.
Fabrizio DragoDivision of Cardiovascular Medicine, Department of Medicine, University of Virginia, Charlottesville, VA, USA.
Marcella MaWellcome-MRC Institute of Metabolic Science and Medical Research Council Metabolic Diseases Unit, University of Cambridge, UK.
Maria Ozsvar KozmaDepartment of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.
Froher YasinDepartment of Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.
Yuta SaadyDepartment of Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.
Hema KothariDivision of Cardiovascular Medicine, Department of Medicine, University of Virginia, Charlottesville, VA, USA.ORCID 0000-0002-9702-5233
Tian X ZhaoDepartment of Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.
Guo-Ping ShiDepartment of Medicine, Brigham and Woman's Hospital, Harvard Medical School, Boston, MA, USA.ORCID 0000-0001-5809-2567
Coleen A McNamaraDivision of Cardiovascular Medicine, Department of Medicine, University of Virginia, Charlottesville, VA, USA.
Christoph J BinderDepartment of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.
Andrew P SageDepartment of Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.
Jason M TarkinDepartment of Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.ORCID 0000-0002-9132-120X
Ziad MallatDepartment of Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.ORCID 0000-0003-0443-7878
Meritxell NusDepartment of Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK.ORCID 0000-0002-6378-8910
University of Cambridge · GBUniversity of Virginia · USHarvard University · USInserm · FRMedical University of Vienna · AT

Funding

Project 4: APOB-specific CD4 and CD8 T cells exacerbate atherosclerosisP01HL136275 · NHLBI · LA JOLLA INSTITUTE FOR IMMUNOLOGY · PI Catherine C Hedrick · 2017 to 2026
$25.5M
British Heart Foundation FS/20/23/34784British Heart Foundation FS/CRTF/20/24035British Heart Foundation PG/17/73/33251British Heart Foundation PG/22/10898NHLBI NIH HHS P01 HL136275Wellcome TrustWellcome Trust 211100/Z/18/Z
6 · The paper itself

Abstract

aimsThe adaptive immune response plays an important role in atherosclerosis. In response to a high-fat/high-cholesterol (HF/HC) diet, marginal zone B (MZB) cells activate an atheroprotective programme by regulating the differentiation and accumulation of 'poorly differentiated' T follicular helper (Tfh) cells. On the other hand, Tfh cells activate the germinal centre response, which promotes atherosclerosis through the production of class-switched high-affinity antibodies. We therefore investigated the direct role of Tfh cells and the role of IL18 in Tfh differentiation in atherosclerosis. METHODS AND

resultsWe generated atherosclerotic mouse models with selective genetic deletion of Tfh cells, MZB cells, or IL18 signalling in Tfh cells. Surprisingly, mice lacking Tfh cells had increased atherosclerosis. Lack of Tfh not only reduced class-switched IgG antibodies against oxidation-specific epitopes (OSEs) but also reduced atheroprotective natural IgM-type anti-phosphorylcholine (PC) antibodies, despite no alteration of natural B1 cells. Moreover, the absence of Tfh cells was associated with an accumulation of MZB cells with substantially reduced ability to secrete antibodies. In the same manner, MZB cell deficiency in Ldlr-/- mice was associated with a significant decrease in atheroprotective IgM antibodies, including natural anti-PC IgM antibodies. In humans, we found a positive correlation between circulating MZB-like cells and anti-OSE IgM antibodies. Finally, we identified an important role for IL18 signalling in HF/HC diet-induced Tfh.

conclusionOur findings reveal a previously unsuspected role of MZB cells in regulating atheroprotective 'natural' IgM antibody production in a Tfh-dependent manner, which could have important pathophysiological and therapeutic implications.

Indexed as

AtherosclerosisInterleukin-18AnimalsB-LymphocytesCholesterolHumansImmunoglobulin MMiceT-Lymphocytes, Helper-InducerCholesterolImmunoglobulin MInterleukin-18AntibodiesAtherosclerosisB cellsInterleukin-18T cells

Identifiers

PMID38381113
PMCPMC10939463
OpenAlexW4391994533

What OpenQuestion holds

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LicenceCC BY
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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.