Staphylococcal toxin induced preferential and prolonged in vivo deletion of innate-like B lymphocytes.
Contributing to host defenses from the adaptive immune system, splenic marginal zone (MZ) B cells, with their preactivated state and special topographical location, serve essential roles as primary defenders from blood-borne microbes. From studies designed to define the immunologic impact of protein A of Staphylococcus aureus (SpA), a virulence factor with targeted B cell antigen receptor-binding properties, we found that within minutes of in vivo exposure, SpA became surface associated with B lymphocytes and induced trafficking. Within several hours, MZ were completely effaced of affected B cells. This was rapidly followed by massive B cell apoptosis, with accelerated preferential deletion of targeted MZ B cells and impaired responsiveness to T independent immunogens. Subsequently, the temporal recovery of MZ B cells was significantly delayed compared to peripheral follicular B cells (B-2 cells). These studies elucidate the cellular program induced by a natural toxin that is shown to be highly efficient at depleting innate-like B cells important for defense from systemic infection.
Goodyear
Carl S
CS
Rheumatic Disease Core Center, Department of Medicine, University of California at San Diego, La Jolla, CA 92093-0663, USA.
Silverman
Gregg J
GJ
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000166:cytology* / Q000276:immunology; D013205:Staphylococcal Protein A / Q000633:toxicity*; D013950:Thymus Gland / Q000276:immunology
D013205:Staphylococcal Protein A