Differential effects of staphylococcal toxic shock syndrome toxin-1 on B cell apoptosis

Michaël F Hofer; Karen Newell; Richard C Duke; Patrick M Schlievert; John H Freed; Donald Y M Leung

doi:10.1073/pnas.93.11.5425

Back

Differential effects of staphylococcal toxic shock syndrome toxin-1 on B cell apoptosis

Journal article

Open access

Peer reviewed

Differential effects of staphylococcal toxic shock syndrome toxin-1 on B cell apoptosis

Michaël F Hofer, Karen Newell, Richard C Duke, Patrick M Schlievert, John H Freed and Donald Y M Leung

Proceedings of the National Academy of Sciences - PNAS, Vol.93(11), pp.5425-5430

05/28/1996

DOI: 10.1073/pnas.93.11.5425

PMCID: PMC39262

PMID: 8643591

Files and links (1)

url

https://doi.org/10.1073/pnas.93.11.5425View

Published (Version of record) Open Access

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.

Details

Title: Subtitle: Differential effects of staphylococcal toxic shock syndrome toxin-1 on B cell apoptosis
Creators: Michaël F Hofer - Division of Pediatric Allergy-Immunology, The National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206, USA
Karen Newell - Division of Pediatric Allergy-Immunology, The National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206, USA
Richard C Duke - University of Colorado Health
Patrick M Schlievert - University of Minnesota Medical School
John H Freed - Division of Pediatric Allergy-Immunology, The National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206, USA
Donald Y M Leung - Division of Pediatric Allergy-Immunology, The National Jewish Center for Immunology and Respiratory Medicine, Denver, CO 80206, USA
Resource Type: Journal article
Publication Details: Proceedings of the National Academy of Sciences - PNAS, Vol.93(11), pp.5425-5430
DOI: 10.1073/pnas.93.11.5425
PMID: 8643591
PMCID: PMC39262
NLM abbreviation: Proc Natl Acad Sci U S A
ISSN: 0027-8424
eISSN: 1091-6490
Publisher: National Academy of Sciences
Language: English
Date published: 05/28/1996
Academic Unit: Microbiology and Immunology; Internal Medicine
Record Identifier: 9984001154802771

Metrics

13 Record Views

46 Times Cited - Web of Science