The staphylococcal toxic shock syndrome toxin 1 triggers B cell proliferation and differentiation via major histocompatibility complex-unrestricted cognate T/B cell interaction.
The Staphylococcus aureus exotoxin toxic shock syndrome toxin 1 (TSST-1) is a potent activator of T cells and monocytes. We have recently demonstrated that TSST-1 is a superantigen that binds monomorphic determinants on MHC class II molecules. In the present study, we have examined the effect of TSST-1 on the activation and differentiation of high density human tonsillar B cells. TSST-1 bound to tonsilar B cells with high affinity and saturation kinetics. This binding was effectively inhibited by a combination of anti-HLA-DR and anti-HLA-DQ mAbs. Treatment of purified B cells with TSST-1 failed to induce B cell proliferation or Ig production. However, in the presence of irradiated T cells, TSST-1 induced resting B cells to proliferate and differentiate into Ig secretory cells. TSST-1 mimicked nominal antigen in that its induction of B cell responses was strictly dependent on physical contact between T and B cells, and was profoundly inhibited by anti-MHC class II mAbs, anti-CD3 mAbs, and, to a lesser extent, by anti-CD18 mAbs. However, unlike nominal antigen, TSST-1-mediated T/B cell interactions were MHC unrestricted. These results suggest that TSST-1 induces T cell-dependent B cell proliferation and differentiation by virtue of its ability to mediate MHC-unrestricted cognate T/B cell interaction via the TCR/CD3 complex and MHC class II antigens.
Mourad
W
W
Division of Immunology, Childrens Hospital, Boston, Massachusetts.
Scholl
P
P
Diaz
A
A
Geha
R
R
Chatila
T
T
D000911:Antibodies, Monoclonal / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D001427:Bacterial Toxins; D002450:Cell Communication / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D004768:Enterotoxins / Q000378:metabolism / Q000633:toxicity*; D000949:Histocompatibility Antigens Class II / Q000502:physiology*; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects*; D013211:Staphylococcus aureus / Q000472:pathogenicity*; D018089:Superantigens; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology
D000911:Antibodies, Monoclonal; D001427:Bacterial Toxins; D004768:Enterotoxins; D000949:Histocompatibility Antigens Class II; D007136:Immunoglobulins; D018089:Superantigens; C030107:enterotoxin F, Staphylococcal