Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 101, Issue 31, Pages 11392-11397Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0404382101
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Funding
- NCI NIH HHS [R21 CA104815, CA104815] Funding Source: Medline
- NIAID NIH HHS [AI40305, AI46637, R01 AI040305] Funding Source: Medline
- NIAMS NIH HHS [P30 AR047360, AR47360, R21 AR050659, AR50659] Funding Source: Medline
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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.
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