Polyclonal B-cell activation by an arthritogenic Staphylococcus aureus strain: contribution of T-cells and monokines.
We have recently described a murine model of Staphylococcus aureus-induced septic arthritis. One of the hallmarks of this disease is a striking hypergammaglobulinemia. In the present study we have used a sensitive ELISPOT technique to assess, at the single cell level, the B-cell differentiation properties of this arthritogenic, toxic shock syndrome toxin-1 (TSST-1)-producing staphylococcal strain. In vivo, inoculation of live S. aureus resulted in lymphoproliferation, early (within 3-4 days) peak of IgM-secreting cells and late (2 weeks after the injection) pronounced increase of IgG-secreting cells. We have documented that this late increase of IgG-secreting cells is a CD4+ T-cell-dependent phenomenon. Furthermore, we have showed that there is a relationship between the hypergammaglobulinemia and the appearance of arthritis, since a nonarthritogenic staphylococcal strain will not give rise to increased frequency of immunoglobulin-secreting cells. To elucidate mechanisms responsible for S. aureus-induced polyclonal B-cell activation, we have assessed in vitro effects of formalin-fixed arthritogenic S. aureus on the release of cytokines. Our results show that the S. aureus LS-1 strain induces in vitro preferentially IgM-secreting cells, many of them displaying autoantibody properties. The magnitude of this response is high and comparable with optimal concentrations of LPS, a potent murine polyclonal B-cell activator. Interleukin-1 alpha (IL-1 alpha), tumor necrosis factor (TNF), and interleukin-6 (IL-6) were all secreted by mouse MNC after in vitro exposure to formalin-killed S. aureus. Inhibition experiments, using neutralizing antibodies to these cytokines, revealed that IL-1 alpha and IL-6 but not TNF-alpha had potent B-cell differentiation properties in S. aureus-stimulated cell cultures.
Abdelnour
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Department of Clinical Immunology, University of Göteborg, Sweden.
Tarkowski
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D000818:Animals; D000917:Antibody Formation; D001169:Arthritis, Experimental / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000187:drug effects; D002473:Cell Wall / Q000276:immunology; D007375:Interleukin-1 / Q000502:physiology; D015850:Interleukin-6 / Q000502:physiology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D015846:Monokines / Q000502:physiology*; D013154:Spleen / Q000166:cytology; D013211:Staphylococcus aureus / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D007375:Interleukin-1; D015850:Interleukin-6; D015846:Monokines; D014409:Tumor Necrosis Factor-alpha