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Published online before print July 18, 2007

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(Journal of Leukocyte Biology. 2007;82:813-820.)
© 2007 by Society for Leukocyte Biology

Differential effects of Francisella tularensis lipopolysaccharide on B lymphocytes

Riad M. Rahhal^*, Tony J. Vanden Bush, Molly K. McLendon, Michael A. Apicella and Gail A. Bishop^,,1

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

¹ Correspondence: Department of Microbiology, Immunology Graduate Program, Department of Internal Medicine, Holden Cancer Center, University of Iowa and Veterans Affairs Medical Center, 2193B Medical Education and Research Facility, University of Iowa, Iowa City, IA 52242, USA. 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-, 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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