Staphylococcal toxin induced preferential and prolonged in vivo deletion of innate-like B lymphocytes
- Rheumatic Disease Core Center, Department of Medicine, University of California at San Diego, La Jolla, CA 92093-0663
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Communicated by J. Edwin Seegmiller, University of California at San Diego, La Jolla, CA, June 18, 2004 (received for review May 20, 2002)
Abstract
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.
Footnotes
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↵ * To whom correspondence should be addressed. E-mail: gsilverman{at}ucsd.edu.
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Abbreviations: Ag, antigen; BCR, B cell receptor; MZ, marginal zone; SAg, super-Ag; SpA, protein A of Staphylococcus aureus; TI, thymic independent; TNP, 2,4,6-trinitrophenyl; B-2, peripheral follicular B cells; T1, type 1.
- Copyright © 2004, The National Academy of Sciences
