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Published online before print July 18, 2007
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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.1206765

Received for publication December 21, 2006.
Revised June 22, 2007.
Accepted for publication June 28, 2007.

Article

Differential effects of Francisella tularensis lipopolysaccharide on B lymphocytes

Riad M. Rahhal *, Tony J. VandenBush {dagger}, Molly K. McLendon {dagger}, Michael A. Apicella {dagger}, and Gail A. Bishop {dagger}{ddagger}@

Departments of *Pediatrics and {dagger}Microbiology, University of Iowa, and {ddagger}Immunology Graduate Program, Department of Internal Medicine, Holden Cancer Center, University of Iowa and Veterans Affairs Medical Center, Iowa City, Iowa, USA

@ To whom correspondence should be addressed. E-mail: gail-bishop{at}uiowa.edu.


  Abstract

Francisella tularensis, a designated Category A biological agent, can cause severe infection in humans. Previous studies have demonstrated a significant immunoprotective role for B lymphocytes in animal models, but the responses of human B lymphocytes to F. tularensis components are largely unknown. The LPS of F. tularensis is atypical and has been reported to lack biological activity on myeloid cells and mouse B cells. Our study characterized the immunological effects of highly purified LPS from different stains of F. tularensis on human B lymphocytes and compared these effects with those on mouse B cells and human monocyte-derived macrophages. Results indicate that marked differences exist between cell type and species in specific responses to this interesting bacterial component. In sharp contrast to responses of mouse splenic B cells or human macrophages, human peripheral B cells showed reproducibly elevated IL-6, TNF-{alpha}, and antibody production in response to F. tularensis LPS. Data also indicated that these activated human B lymphocytes may subsequently promote the activation of other immune cell types by direct cell-cell interaction. Further investigation into the potential usefulness of F. tularensis LPS as an adjuvant component of a more optimal subunit vaccine is warranted, as it is now clear that it is not biologically inactive, as assumed previously.

Key Words: B cell immunology • human • tularemia • bacterial components




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