Evidence map›Paper›PMID 33563755›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2021

CD20 as a gatekeeper of the resting state of human B cells.

Kathrin Kläsener, Julia Jellusova, Geoffroy Andrieux, Ulrich Salzer, Chiara Böhler, Sebastian N Steiner, Jonas B Albinus, Marco Cavallari, Beatrix Süß, Reinhard E Voll and 3 more

Open access · hybridAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
75citing papers in PubMed, 1 pooled it
6.6field-weighted citation impact, top 2% 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

75 citing papers in PubMed, 1 synthesis or guideline pooled it, 113 citations in OpenAlex.

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15 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 3 institutions in 2 countries.

Kathrin KläsenerBiology III, Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany.ORCID 0000-0002-5969-2553
Julia JellusovaBiology III, Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany.
Geoffroy Andrieuxlnstitute of Medical Bioinformatics and Systems Medicine, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, 79110 Freiburg, Germany.ORCID 0000-0002-5389-9481
Ulrich SalzerDepartment of Rheumatology and Clinical Immunology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany.
Chiara BöhlerBiology III, Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany.
Sebastian N SteinerDepartment of Health Sciences and Technology, Institute of Translational Medicine, Swiss Federal Institute of Technology, ETH Zürich, 8093 Zurich, Switzerland.ORCID 0000-0002-1281-8403
Jonas B AlbinusDepartment of Health Sciences and Technology, Institute of Translational Medicine, Swiss Federal Institute of Technology, ETH Zürich, 8093 Zurich, Switzerland.
Marco CavallariBiology III, Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany.
Beatrix SüßDepartment of Biology, Centre for Synthetic Biology, Technical University Darmstadt, 64289 Darmstadt, Germany.
Reinhard E VollDepartment of Rheumatology and Clinical Immunology, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany.
Melanie Boerrieslnstitute of Medical Bioinformatics and Systems Medicine, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, 79110 Freiburg, Germany.
Bernd WollscheidDepartment of Health Sciences and Technology, Institute of Translational Medicine, Swiss Federal Institute of Technology, ETH Zürich, 8093 Zurich, Switzerland.ORCID 0000-0002-3923-1610
Michael RethBiology III, Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany; michael.reth@bioss.uni-freiburg.de.ORCID 0000-0002-1025-7198
University of Freiburg · DESIB Swiss Institute of Bioinformatics · CHTechnische Universität Darmstadt · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

CD20 is a B cell-specific membrane protein and represents an attractive target for therapeutic antibodies. Despite widespread usage of anti-CD20 antibodies for B cell depletion therapies, the biological function of their target remains unclear. Here, we demonstrate that CD20 controls the nanoscale organization of receptors on the surface of resting B lymphocytes. CRISPR/Cas9-mediated ablation of CD20 in resting B cells resulted in relocalization and interaction of the IgM-class B cell antigen receptor with the coreceptor CD19. This receptor rearrangement led to a transient activation of B cells, accompanied by the internalization of many B cell surface marker proteins. Reexpression of CD20 restored the expression of the B cell surface proteins and the resting state of Ramos B cells. Similarly, treatment of Ramos or naive human B cells with the anti-CD20 antibody rituximab induced nanoscale receptor rearrangements and transient B cell activation in vitro and in vivo. A departure from the resting B cell state followed by the loss of B cell identity of CD20-deficient Ramos B cells was accompanied by a PAX5 to BLIMP-1 transcriptional switch, metabolic reprogramming toward oxidative phosphorylation, and a shift toward plasma cell development. Thus, anti-CD20 engagement or the loss of CD20 disrupts membrane organization, profoundly altering the fate of human B cells.

Indexed as

Antigens, CD19Antigens, CD20B-LymphocytesCell Line, TumorCell MembraneCells, CulturedHumansLymphocyte ActivationReceptors, Antigen, B-CellAntigens, CD19Antigens, CD20Receptors, Antigen, B-CellB lymphocyteCD20plasma celltherapeutic antibody

Identifiers

PMID33563755
PMCPMC7896350
OpenAlexW3127518626

What OpenQuestion holds

Textmetadata
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.