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Cutting Edge: Importance of IL-6 and Cooperation between Innate and Adaptive Immune Receptors in Cellular Vaccination with B Lymphocytes¹

Tony J. Vanden Bush,^* Claire M. Buchta, Jennifer Claudio,² and Gail A. Bishop^3*

^*Department of Microbiology, Immunology Graduate Program, and Department of Internal Medicine, University of Iowa, Iowa City, IA 52242; and Iowa City Veterans Affairs Medical Center, Iowa City, IA 52242

B lymphocytes are a potential alternative to dendritic cell immunotherapy, with the advantages of relative abundance in peripheral blood and the ability to function as APCs. Although B cells express multiple receptors that induce costimulatory molecules, B cell vaccine studies have focused primarily on CD40 stimulation. To optimize the potential efficacy of B cell vaccines (Bvac), we compared the capacity of differentially stimulated B cells to induce Ag-specific CD8⁺ T cell responses in vivo. CD40- or TLR7-stimulated B cell APCs induced similar CD8⁺ T cell responses, but costimulation through the BCR and TLR7 produced a more effective Bvac as measured by T cell stimulation and the protection of mice from an infectious pathogen. This increased effectiveness depended upon enhanced production of IL-6 by BCR plus TLR7-stimulated B cells. These findings reveal alternative stimulation strategies for the production of effective Bvac and identify a key role for IL-6 in B cell Ag presentation and cellular vaccines.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This material is based upon work supported in part by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development and Health, Services Research and Development, Merit Review Award 383 (to G.A.B.). T.J.V.B. received support from an American Cancer Society postdoctoral fellowship (PF-07-067-01-LIB).

² Current address: Department of Chemistry, Pontifical Catholic University of Puerto Rico, Ponce, Puerto Rico.

³ Address correspondence and reprint requests to Dr. Gail Bishop, 2193 Medical Education Research Facility, Department of Biology, University of Iowa, Iowa City 52242. E-mail address: gail-bishop{at}uiowa.edu

⁴ Abbreviations used in this paper: DC, dendritic cell; Bvac, B cell vaccine; LM, L. monocytogenes; LMA, attenuated L. monocytogenes.

⁵ The online version of this article contains supplemental material.