Evidence map›Paper›PMID 31204070›Full record

ArticleImmunity2019

The HVEM-BTLA Axis Restrains T Cell Help to Germinal Center B Cells and Functions as a Cell-Extrinsic Suppressor in Lymphomagenesis.

Michelle A Mintz, James H Felce, Marissa Y Chou, Viveka Mayya, Ying Xu, Jr-Wen Shui, Jinping An, Zhongmei Li, Alexander Marson, Takaharu Okada and 4 more

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

Article in Immunity, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
71citing papers in PubMed, 1 pooled it
5.1field-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

71 citing papers in PubMed, 1 synthesis or guideline pooled it, 99 citations in OpenAlex.

  1. Pooled it
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  13. A multi-omics integrative analyses revealsFrontiers in pharmacology · 2026
    Article
  14. MutantFrontiers in immunology · 2026
    Article
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11 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 6 institutions in 3 countries.

Michelle A MintzDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA, USA.
James H FelceKennedy Institute of Rheumatology, University of Oxford, Oxford, UK.
Marissa Y ChouDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA, USA.
Viveka MayyaKennedy Institute of Rheumatology, University of Oxford, Oxford, UK.
Ying XuDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA, USA.
Jr-Wen ShuiDivision of Developmental Immunology, La Jolla Institute for Immunology, La Jolla, CA, USA.
Jinping AnDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA, USA.
Zhongmei LiDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA.
Alexander MarsonDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA.
Takaharu OkadaRIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan.
Carl F WareInfectious and Inflammatory Diseases Center, Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA, USA.
Mitchell KronenbergDivision of Developmental Immunology, La Jolla Institute for Immunology, La Jolla, CA, USA.
Michael L DustinKennedy Institute of Rheumatology, University of Oxford, Oxford, UK.
Jason G CysterDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA, USA. Electronic address: jason.cyster@ucsf.edu.
Howard Hughes Medical Institute · USUniversity of Oxford · GBLa Jolla Institute for Immunology · USUniversity of California, San Francisco · USRIKEN Center for Integrative Medical Sciences · JPSanford Burnham Prebys Medical Discovery Institute · US

Funding

Using polygenic scores to enhance both variant discovery, and understanding of functional consequences of genetic variation in IBD.P01DK046763 · NIDDK · CEDARS-SINAI MEDICAL CENTER · PI TARGAN, STEPHAN R. · 1992 to 2020
$31.1M
MEDICAL SCIENTIST TRAINING PROGRAMT32GM007618 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ANDERSON, MARK S · 1985 to 2020
$29.6M
Chemokines and Lymphoid Tissue Organization and FunctionR01AI045073 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CYSTER, JASON G · 1999 to 2023
$7.6M
HVEM: A TNF family receptor that influences mucosal immunity and the microbiomeU01AI125955 · NIAID · LA JOLLA INSTITUTE FOR IMMUNOLOGY · PI KRONENBERG, MITCHELL · 2016 to 2020
$2.7M
Chemokines and Lymphoid Tissue Organization and FunctionR37AI045073 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Jason G Cyster · 2024 to 2026
$1.7M
Dissecting the role of HVEM and BTLA in constraining the germinal center B cell responseF30AI131496 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MINTZ, MICHELLE · 2017 to 2020
$160k
NIAID NIH HHS F30 AI131496NIAID NIH HHS R01 AI045073NIAID NIH HHS R37 AI045073NIAID NIH HHS U01 AI125955NIDDK NIH HHS P01 DK046763NIGMS NIH HHS T32 GM007618Wellcome TrustWellcome Trust 100262Z/12/ZWellcome Trust 107375/Z/15/Z
6 · The paper itself

Abstract

The tumor necrosis factor receptor superfamily member HVEM is one of the most frequently mutated surface proteins in germinal center (GC)-derived B cell lymphomas. We found that HVEM deficiency increased B cell competitiveness during pre-GC and GC responses. The immunoglobulin (Ig) superfamily protein BTLA regulated HVEM-expressing B cell responses independently of B-cell-intrinsic signaling via HVEM or BTLA. BTLA signaling into T cells through the phosphatase SHP1 reduced T cell receptor (TCR) signaling and preformed CD40 ligand mobilization to the immunological synapse, thus diminishing the help delivered to B cells. Moreover, T cell deficiency in BTLA cooperated with B cell Bcl-2 overexpression, leading to GC B cell outgrowth. These results establish that HVEM restrains the T helper signals delivered to B cells to influence GC selection outcomes, and they suggest that BTLA functions as a cell-extrinsic suppressor of GC B cell lymphomagenesis.

Indexed as

AnimalsB-LymphocytesCell ProliferationGerminal CenterImmunological SynapsesLymphocyte ActivationMiceMice, KnockoutMice, TransgenicParacrine CommunicationProtein Tyrosine Phosphatase, Non-Receptor Type 6Proto-Oncogene Proteins c-bcl-2Receptors, Antigen, T-CellReceptors, ImmunologicReceptors, Tumor Necrosis Factor, Member 14Signal TransductionBcl2 protein, mouseBTLA protein, mouseProtein Tyrosine Phosphatase, Non-Receptor Type 6Proto-Oncogene Proteins c-bcl-2Receptors, Antigen, T-CellReceptors, ImmunologicReceptors, Tumor Necrosis Factor, Member 14

Identifiers

PMID31204070
PMCPMC6703922
OpenAlexW2951843883

What OpenQuestion holds

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LicenceCC BY
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.