Engagement of MHC-class II molecules by staphylococcal exotoxins delivers a comitogenic signal to human B cells.
The staphylococcal exotoxin toxic shock syndrome toxin-1 (TSST-1) has been demonstrated to bind to monomorphic determinants on MHC-class II molecules. In this study, we have used TSST-1 to probe the role of MHC-class II molecules in the activation and differentiation of resting human B cells. Highly purified B cells were stimulated with TSST-1, alone or in combination with PMA or with anti-human IgM antibodies (anti-mu) and the resulting B cell proliferation and Ig production were monitored. On its own, TSST-1 failed to induce B cell proliferation or Ig production. However, TSST-1 synergized with PMA and with anti-mu in inducing B cell proliferation in the absence of any added T cells or T cell factors. TSST-1 did not induce or potentiate early activation events associated with anti-mu treatment such as phosphoinositide hydrolysis and Ca2+ mobilization. Also, TSST-1 did not potentiate the capacity of anti-mu to induce the transcription of early activation genes such as c-myc. Finally, in contrast to its capacity to promote mitogen-trigered B cell proliferation, TSST-1 failed to induce the differentiation of B lymphocytes into Ig-secreting cells in the absence of added T cells. These results indicate that TSST-1 delivers a comitogenic signal to B cells via MHC-class II molecules that is distinct from signals delivered via surface mu and further strengthens the role of MHC-class II molecules as signal transducing structures.
Fuleihan
R
R
Division of Immunology, Children's Hospital Boston, MA 02115.
Mourad
W
W
Geha
R S
RS
Chatila
T
T
D000888:Antibodies, Anti-Idiotypic; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D001427:Bacterial Toxins; D000242:Cyclic AMP / Q000378:metabolism; D004768:Enterotoxins / Q000276:immunology*; D005098:Exotoxins / Q000276:immunology*; D006681:HLA-D Antigens / Q000502:physiology*; D006801:Humans; D007148:Immunoglobulin mu-Chains / Q000502:physiology; D008213:Lymphocyte Activation / Q000187:drug effects; D008934:Mitogens; D015398:Signal Transduction / Q000276:immunology*; D018089:Superantigens; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000888:Antibodies, Anti-Idiotypic; D001427:Bacterial Toxins; D004768:Enterotoxins; D005098:Exotoxins; D006681:HLA-D Antigens; D007148:Immunoglobulin mu-Chains; D008934:Mitogens; D018089:Superantigens; C030107:enterotoxin F, Staphylococcal; D000242:Cyclic AMP; D013755:Tetradecanoylphorbol Acetate