Cutting Edge: Importance of IL-6 and cooperation between innate and adaptive immune receptors in cellular vaccination with B lymphocytes.
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.
Department of Microbiology, University of Iowa, Iowa City, IA 52242, USA.
Tony J
TJ
Vanden Bush
Claire M
CM
Buchta
Jennifer
J
Claudio
Gail A
GA
Bishop
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000382:microbiology / Q000637:transplantation*; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology; D015850:Interleukin-6 / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D008089:Listeria monocytogenes / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D011947:Receptors, Antigen, B-Cell / Q000276:immunology / Q000378:metabolism; D051199:Toll-Like Receptor 7 / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism; D014611:Vaccination; D014612:Vaccines / Q000276:immunology*
D015850:Interleukin-6; D008562:Membrane Glycoproteins; D011947:Receptors, Antigen, B-Cell; C477038:Tlr7 protein, mouse; D051199:Toll-Like Receptor 7; D014409:Tumor Necrosis Factor-alpha; D014612:Vaccines; D010047:Ovalbumin