CD20 is gatekeeper of human B cell identity and activation state
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ABSTRACT: 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.
INSTRUMENT(S): Q Exactive HFX (Thermo Scientific Instrument Model)
ORGANISM(S): Homo Sapiens (ncbitaxon:9606)
SUBMITTER: Bernd Wollscheid
PROVIDER: MSV000085605 | MassIVE | Thu Jun 18 06:38:00 BST 2020
SECONDARY ACCESSION(S): PXD019874
REPOSITORIES: MassIVE
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