CD20 as a gatekeeper of the resting state of human B cells

Proc Natl Acad Sci U S A. 2021 Feb 16;118(7):e2021342118. doi: 10.1073/pnas.2021342118.


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.

Keywords: B lymphocyte; CD20; plasma cell; therapeutic antibody.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD19 / metabolism
  • Antigens, CD20 / metabolism*
  • B-Lymphocytes / immunology*
  • Cell Line, Tumor
  • Cell Membrane / metabolism
  • Cells, Cultured
  • Humans
  • Lymphocyte Activation
  • Receptors, Antigen, B-Cell / metabolism


  • Antigens, CD19
  • Antigens, CD20
  • Receptors, Antigen, B-Cell