Evidence map›Paper›PMID 31365872›Full record

ArticleCell reports2019

CRISPR/Cas9 Screens Reveal Multiple Layers of B cell CD40 Regulation.

Chang Jiang, Stephen J Trudeau, Taek-Chin Cheong, Rui Guo, Mingxiang Teng, Liang Wei Wang, Zhonghao Wang, Chiara Pighi, Carole Gautier-Courteille, Yijie Ma and 7 more

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
1.2field-weighted citation impact, top 19% 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

24 citing papers in PubMed, 38 citations in OpenAlex.

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  7. Arginine Metabolism SupportsbioRxiv : the preprint server for biology · 2025
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  12. Methylation of T and B Lymphocytes in Autoimmune Rheumatic Diseases.Clinical reviews in allergy & immunology · 2024
    Review
  13. Review
  14. FBXO11 constitutes a major negative regulator of MHC class II through ubiquitin-dependent proteasomal degradation of CIITA.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  15. Review
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  17. Article
  18. The Role of mInternational journal of molecular sciences · 2023
    Review
  19. Gene editing and its applications in biomedicine.Science China. Life sciences · 2022
    Review
  20. CRISPR Screens to Identify Regulators of Tumor Immunity.Annual review of cancer biology · 2022
    Article
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

17 authors at 6 institutions in 4 countries.

Chang JiangDivision of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, 181 Longwood Avenue, Boston, MA 02115, USA; Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA.
Stephen J TrudeauDivision of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, 181 Longwood Avenue, Boston, MA 02115, USA; Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA.
Taek-Chin CheongDepartment of Pathology, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA.
Rui GuoDivision of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, 181 Longwood Avenue, Boston, MA 02115, USA; Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA.
Mingxiang TengDepartment of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.
Liang Wei WangDivision of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, 181 Longwood Avenue, Boston, MA 02115, USA; Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA; Graduate Program in Virology, Division of Medical Sciences, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
Zhonghao WangDivision of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, 181 Longwood Avenue, Boston, MA 02115, USA; Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA; Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
Chiara PighiDepartment of Pathology, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Carole Gautier-CourteilleBiosit, Université de Rennes 1, 35043 Rennes, France; Centre National de la Recherche Scientifique UMR 6290, Institut de Génétique et Développement de Rennes, 35043 Rennes, France.
Yijie MaDivision of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, 181 Longwood Avenue, Boston, MA 02115, USA; Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA.
Sizun JiangDivision of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, 181 Longwood Avenue, Boston, MA 02115, USA; Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA; Graduate Program in Virology, Division of Medical Sciences, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
Chong WangDivision of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, 181 Longwood Avenue, Boston, MA 02115, USA.
Bo ZhaoDivision of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, 181 Longwood Avenue, Boston, MA 02115, USA.
Luc PaillardBiosit, Université de Rennes 1, 35043 Rennes, France; Centre National de la Recherche Scientifique UMR 6290, Institut de Génétique et Développement de Rennes, 35043 Rennes, France.
John G DoenchBroad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
Roberto ChiarleDepartment of Pathology, Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA; Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy.
Benjamin E GewurzDivision of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, 181 Longwood Avenue, Boston, MA 02115, USA; Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA; Department of Biostatistics and Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA. Electronic address: bgewurz@bwh.harvard.edu.
Brigham and Women's Hospital · USHarvard University · USBoston Children's Hospital · USInstitut de génétique et de développement de Rennes · FRBroad Institute · USMoffitt Cancer Center · US

Funding

TRANSLATIONAL RESEARCHP30CA076292 · NCI · UNIVERSITY OF SOUTH FLORIDA · PI John L. Cleveland · 1998 to 2026
$93.5M
Targeting Epstein-Barr Virus super-enhancersR01AI123420 · NIAID · BRIGHAM AND WOMEN'S HOSPITAL · PI Bo Zhao · 2016 to 2026
$5.1M
Mechanisms of resistance to ALK inhibitors in ALK-rearranged lymphomaR01CA196703 · NCI · BOSTON CHILDREN'S HOSPITAL · PI CHIARLE, ROBERTO · 2015 to 2025
$4.1M
Metabolic Network Remodeling in Epstein-Barr Virus LymphomagenesisR01AI137337 · NIAID · BRIGHAM AND WOMEN'S HOSPITAL · PI GEWURZ, BENJAMIN ELISON · 2018 to 2022
$2.2M
Howard Hughes Medical InstituteNCI NIH HHS P30 CA076292NCI NIH HHS R01 CA196703NIAID NIH HHS R01 AI123420NIAID NIH HHS R01 AI137337
6 · The paper itself

Abstract

CD40 has major roles in B cell development, activation, and germinal center responses. CD40 hypoactivity causes immunodeficiency whereas its overexpression causes autoimmunity and lymphomagenesis. To systematically identify B cell autonomous CD40 regulators, we use CRISPR/Cas9 genome-scale screens in Daudi B cells stimulated by multimeric CD40 ligand. These highlight known CD40 pathway components and reveal multiple additional mechanisms regulating CD40. The nuclear ubiquitin ligase FBXO11 supports CD40 expression by targeting repressors CTBP1 and BCL6. FBXO11 knockout decreases primary B cell CD40 abundance and impairs class-switch recombination, suggesting that frequent lymphoma monoallelic FBXO11 mutations may balance BCL6 increase with CD40 loss. At the mRNA level, CELF1 controls exon splicing critical for CD40 activity, while the N6-adenosine methyltransferase WTAP negatively regulates CD40 mRNA abundance. At the protein level, ESCRT negatively regulates activated CD40 levels while the negative feedback phosphatase DUSP10 limits downstream MAPK responses. These results serve as a resource for future studies and highlight potential therapeutic targets.

Indexed as

CRISPR-Cas SystemsMAP Kinase Signaling SystemAlcohol OxidoreductasesB-LymphocytesCD40 AntigensCELF1 ProteinCell Line, TumorDNA-Binding ProteinsDual-Specificity PhosphatasesF-Box ProteinsHumansMitogen-Activated Protein Kinase PhosphatasesProtein-Arginine N-MethyltransferasesProto-Oncogene Proteins c-bcl-6Alcohol OxidoreductasesBCL6 protein, humanCD40 AntigensCELF1 ProteinCELF1 protein, humanC-terminal binding proteinDNA-Binding ProteinsDual-Specificity PhosphatasesDUSP10 protein, humanF-Box ProteinsFBXO11 protein, humanMitogen-Activated Protein Kinase PhosphatasesProtein-Arginine N-MethyltransferasesProto-Oncogene Proteins c-bcl-6B cell activationCRISPR screenESCRTgerminal centerhumoral immunityimmunodeficiencyMAP kinaseN6-MethyladenosineNF-kappaBTNF receptor superfamily

Identifiers

PMID31365872
PMCPMC6684324
OpenAlexW2966567262

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.