MassIVE MSV000085605

Complete Public PXD019874

CD20 is gatekeeper of human B cell identity and activation state

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Description

B cell identity and function is dependent on the proteins residing in the B cell surfaceome and their respective nanoscale organization. Here we show that CD20 is a gatekeeper for B cell identity and function due to its control of the functional nanoscale organization of receptors within the B surfaceome and the resting state of B lymphocytes. CRISPR/Cas-based ablation of CD20 in Ramos B cells revealed that IgM class B cell antigen receptor (IgM-BCR) and the co-receptor CD19 are functionally interlinked in the absence of CD20. The resulting IgM-BCR/CD19 signalling synapse leads to transient B cell activation and the loss of B cell identity. Re-expression of CD20 involving an aptamer-controlled riboswitch restores resting-state B cell nanoscale organization and function. Treatment of naive human B cells with the anti-CD20 antibody Rituximab leads to transient B cell activation and formation of transiently activated IgM-BCR/CD19 signalling synapses providing new insights into the molecular mode of action of Rituximab. The loss of B cell identity due to CD20-deficiency is accompanied by a PAX5 to BLIMP-1 transcriptional switch and increased plasma cell development. This cellular B cell differentiation towards plasma B cells is mechanistically accompanied by a metabolic shift towards oxidative phosphorylation. [doi:10.25345/C5WX31] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: CD20, B cell, surfaceome

Contact

Principal Investigators:
(in alphabetical order) 		Bernd Wollscheid, Institute of Molecular Systems Biology & Department of Health Sciences and Technology, ETH Zurich, Switzerland, N/A
Submitting User: jalbinus

Publications

Kathrin Kläsener, Julia Jellusova, Geoffroy Andrieux, Ulrich Salzer, Chiara Böhler, Sebastian N Steiner, Jonas B Albinus, Marco Cavallari, Beatrix Süß, Reinhard E Voll, Melanie Boerries, Bernd Wollscheid, Michael Reth.
CD20 as a gatekeeper of the resting state of human B cells.
Kläsener, K. et al. CD20 as a gatekeeper of the resting state of human B cells. Proc. Natl. Acad. Sci. U. S. A. 118, (2021).

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