PT  - JOURNAL ARTICLE
AU  - Kathrin Kläsener
AU  - Julia Jellusova
AU  - Geoffroy Andrieux
AU  - Ulrich Salzer
AU  - Chiara Böhler
AU  - Sebastian N. Steiner
AU  - Jonas B. Albinus
AU  - Marco Cavallari
AU  - Beatrix Süß
AU  - Melanie Boerries
AU  - Reinhard E. Voll
AU  - Bernd Wollscheid
AU  - Michael Reth
TI  - CD20 as a gatekeeper of the resting stage of human B cells
AID  - 10.1101/2020.07.31.230110
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.07.31.230110
4099  - http://biorxiv.org/content/early/2020/07/31/2020.07.31.230110.short
4100  - http://biorxiv.org/content/early/2020/07/31/2020.07.31.230110.full
AB  - CD20 is a B cell specific membrane protein and a target of therapeutic antibodies such as rituximab (RTX)1. 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, naïve 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.Competing Interest StatementThe authors have declared no competing interest.