Down-modulation of the antigen receptor by a superantigen for human B cells.
B cell superantigens (SAgs) have been implicated in human diseases by demonstrating non-clonotypic expansion of B cells bearing certain immunoglobulin variable region genes. One possibility is that, during infection with microorganisms secreting SAgs, these potent molecules might modulate BcR expression. To test this hypothesis, we investigated the potential effects of a SAg, protein L from Peptostreptococcus magnus, on antigen B cell receptor (BcR) surface expression in vitro. Using fluorescence microscopy, we found that this SAg induced down-regulation of BcR expression. This effect was time-, dose-, and temperature-dependent, and shedding of cell surface IgM molecules into the culture supernatant was not detected. These data demonstrate that SAg-mediated down-regulation of the BcR expression occurs primarily as a result of BcR internalization. In addition, two specific inhibitors of protein tyrosine kinases were found to retard the BcR modulation on the cell surface and inhibit SAg-induced receptor internalization, showing that tyrosine phosphorylation is required for subsequent internalization of mIg-ligand complexes. The down-modulation of BcR expression may have pathological consequences in patients infected with microorganisms secreting SAgs.
Viau
Muriel
M
Institut National de Santé et de Recherche Médicale, Immunopathologie Humaine, 15 rue de l'Ecole de Médecine, 75006 Paris, France.
Cholley
Béatrice
B
Björck
Lars
L
Zouali
Moncef
M
D001402:B-Lymphocytes / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000276:immunology / Q000378:metabolism; D015536:Down-Regulation / Q000276:immunology; D006801:Humans; D007700:Kinetics; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011947:Receptors, Antigen, B-Cell / Q000276:immunology* / Q000502:physiology; D018089:Superantigens / Q000276:immunology*
D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; C116593:L-protein, Peptococcus magnus; D011947:Receptors, Antigen, B-Cell; D018089:Superantigens; D011505:Protein-Tyrosine Kinases