
Open access
Date
2021-02-16Type
- Journal Article
Citations
Cited 19 times in
Web of Science
Cited 20 times in
Scopus
ETH Bibliography
yes
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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. Show more
Permanent link
https://doi.org/10.3929/ethz-b-000472083Publication status
publishedExternal links
Journal / series
Proceedings of the National Academy of Sciences of the United States of AmericaVolume
Pages / Article No.
Publisher
National Academy of SciencesSubject
B lymphocyte; therapeutic antibody; CD20; plasma cellOrganisational unit
02072 - Proteomics Plattform D-HEST
Funding
160259 - Direct identification of lateral protein interactions in the plasma membrane of living cells and tissues (SNF)
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Show all metadata
Citations
Cited 19 times in
Web of Science
Cited 20 times in
Scopus
ETH Bibliography
yes
Altmetrics