title: Differential effects of staphylococcal toxic shock syndrome toxin-1 on B cell apoptosis.
abstract: Superantigens, such as toxic shock syndrome toxin 1 (TSST-1), have been implicated in the pathogenesis of several autoimmune and allergic diseases associated with polyclonal B cell activation. In this report, we studied the in vitro effects of TSST-1 on B cell activation. We show herein that TSST-1 produced antagonistic effects on Ig synthesis by peripheral blood mononuclear cells (PBMC) from normal subjects, depending on the concentration used; Ig production was inhibited at 1000 pg/ml (P < 0.01) and enhanced at 1 and 0.01 pg/ml (P < 0.01) of toxin. Cultures of PBMC were then examined for morphologic features and DNA fragmentation characteristic for apoptosis. B cells exhibited a significantly higher (P < 0.01) incidence of apoptosis after stimulation with 1000 pg/ml of TSST-1 compared with 1 or 0.01 pg/ml of toxin or medium alone. Abundant expression of Fas, a cell surface protein that mediates apoptosis, was detected on B cells after stimulation with 1000 pg/ml of TSST-1 and was significantly higher on B cells undergoing apoptosis than on live cells (P = 0.01). Additionally, increased Fas expression and B cell death occurred at concentrations of TSST-1 inducing the production of high amounts of gamma interferon (IFN-gamma), and both events could be blocked by neutralizing anti-IFN-gamma antibody. These findings suggest that high concentrations of TSST-1 can induce IFN-gamma-dependent B cell apoptosis, whereas at low concentrations it stimulates Ig synthesis by PBMC from normal subjects. These findings support the concept that staphylococcal toxins have a role in B cell hyperactivity in autoimmunity and allergy.
authors.affiliation: Division of Pediatric Allergy-Immunology, The National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206, USA.
authors.forename: M F
authors.initials: MF
authors.lastname: Hofer
authors.forename: K
authors.initials: K
authors.lastname: Newell
authors.forename: R C
authors.initials: RC
authors.lastname: Duke
authors.forename: P M
authors.initials: PM
authors.lastname: Schlievert
authors.forename: J H
authors.initials: JH
authors.lastname: Freed
authors.forename: D Y
authors.initials: DY
authors.lastname: Leung
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D000917:Antibody Formation / Q000187:drug effects; D017209:Apoptosis / Q000187:drug effects*; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D001427:Bacterial Toxins; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004768:Enterotoxins / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology; D007371:Interferon-gamma / Q000276:immunology / Q000502:physiology; D008213:Lymphocyte Activation / Q000187:drug effects*; D018448:Models, Immunological; D011817:Rabbits; D012016:Reference Values; D013211:Staphylococcus aureus; D018089:Superantigens
chemical_list: D000906:Antibodies; D001427:Bacterial Toxins; D004768:Enterotoxins; D007074:Immunoglobulin G; D018089:Superantigens; C030107:enterotoxin F, Staphylococcal; D007371:Interferon-gamma