Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.31.230110v1?rss=1 Authors: Klasener, K., Jellusova, J., Andrieux, G., Salzer, U., Boehler, C., Steiner, S. N., Albinus, J. B., Cavallari, M. F., Suess, B., Boerries, M., Voll, R. E., Wollscheid, B., Reth, M. Abstract: CD20 is a B cell specific membrane protein and a target of therapeutic antibodies such as rituximab (RTX). In spite of the prominent usage of anti-CD20 antibodies in the clinic little is known about the biological function of CD202. Here we show that CD20 controls the nanoscale organization of receptors on the surface of resting B lymphocytes. A CRISPR/Cas-based ablation of CD20 in Ramos B cells results in a relocalisation of the IgM B cell antigen receptor (IgM-BCR) and the co-receptor CD19. The resulting IgM-BCR/CD19 signaling synapse leads to transient B cell activation followed by plasma cell differentiation. Similarly to CD20-deficient Ramos cells, naive human B cells treated with rituximab in vitro or isolated from patients during rituximab administration display hallmarks of transient activation characterized by the formation of the IgM-BCR/CD19 signaling synapse, followed by CD19 and IgM-BCR downregulation. Moreover, increased expression of specific plasma cell genes can be observed after rituximab treatment in relapsed CLL patients. In summary we identify CD20 as a gatekeeper of the resting state on human B cells and demonstrate that a disruption of the nanoscale organization of the B cell surface via CD20 deletion or anti-CD20 treatment profoundly alters B cell fate. Copy rights belong to original authors. Visit the link for more info