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

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Abstract
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 reversed the down‐regulation induced by the CD20 mAb Bl. CD20 most likely triggers a protein kinase C‐dependent pathway to down‐regulate slgM. CD20 mAb also counteracted the interleukin‐4 (IL‐4)‐induced up‐regulation of slgM. The ability of anti‐IgM to mobilize intracellular calcium was reduced in slgM down‐regulated cells, suggesting that B cells activation through the antigen receptor may be negatively regulated by CD20 and positively by IL‐4.

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