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.
Bourget
I
I
Laboratoire d'Immunologie, Cellulaire et Moléculaire INSERM U210, Faculté de Médecine (Pasteur), Nice, France.
Breittmayer
J P
JP
Grenier-Brossette
N
N
Cousin
J L
JL
D000470:Alkaloids / Q000494:pharmacology; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000276:immunology*; D018951:Antigens, CD20; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology*; D001402:B-Lymphocytes / Q000378:metabolism*; D015536:Down-Regulation; D015870:Gene Expression; D005803:Genes, Immunoglobulin; D019833:Genistein; D006801:Humans; D007075:Immunoglobulin M / Q000378:metabolism*; D007148:Immunoglobulin mu-Chains / Q000235:genetics; D066298:In Vitro Techniques; D015847:Interleukin-4 / Q000494:pharmacology; D007529:Isoflavones / Q000494:pharmacology; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger / Q000235:genetics; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D019311:Staurosporine; D013997:Time Factors
D000470:Alkaloids; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D018951:Antigens, CD20; D000944:Antigens, Differentiation, B-Lymphocyte; D007075:Immunoglobulin M; D007148:Immunoglobulin mu-Chains; D007529:Isoflavones; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D011947:Receptors, Antigen, B-Cell; D015847:Interleukin-4; D019833:Genistein; D019311:Staurosporine