CD20 monoclonal antibodies down-regulate IgM at the surface of B cells

The CD20 molecule is a phosphoprotein expressed on the surface of B lymphocytes that plays a role in the regulation of B cell proliferation and differentiation. In this study it was found that monoclonal antibodies (mAb) directed to CD20 decrease the expression of IgM at the surface of normal human B lymphocytes and B cell lines. This effect was time-dependent with a half-time of about 5 h. Incubation of B cells with CD20 mAb B1 did not affect the steady-state level of IgM mRNA, suggesting that it acts at a nontranscriptional stage. Phorbol esters also produced inhibitory effect on surface IgM expression. Staurosporine reversed both the phorbol ester- and the CD20-induced down-regulation. Genistein did not reverse the down-regulation induced by the CD20 mAb B1. CD20 most likely triggers a protein kinase C-dependent pathway to down-regulate sIgM. CD20 mAb also counteracted the interleukin-4 (IL-4)-induced up-regulation of sIgM. The ability of anti-IgM to mobilize intracellular calcium was reduced in sIgM down-regulated cells, suggesting that B cells activation through the antigen receptor may be negatively regulated by CD20 and positively by IL-4.