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Human B Cells Express Functional TRAIL/Apo-2 Ligand after CpG-Containing Oligodeoxynucleotide Stimulation¹

Troy J. Kemp^*,, Jill M. Moore^* and Thomas S. Griffith^2,*,,

^* Department of Urology, Interdisciplinary Graduate Program in Immunology, and Prostate Cancer Research Program of the Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA 52242

CpG-containing oligodeoxynucleotides (CpG ODN) have broad-ranging immunostimulatory effects, including the generation of antitumor immune responses. Analysis of different CpG ODN have identified two classes: CpG-A ODN, which stimulate high levels of IFN- production from plasmacytoid dendritic cells and weakly activate B cells, and CpG-B ODN, which strongly activate B cells but stimulate low production of IFN- from plasmacytoid dendritic cells. Previously, we observed that CpG-B ODN (2006) induces TRAIL/Apo-2 ligand (Apo-2L)-mediated killing of tumor cells by CD14⁺ PBMC. In this study, we extend our investigation of CpG ODN-induced TRAIL/Apo-2L expression and activity in PBMC to include CpG-A ODN. Of the two classes, IFN- production and TRAIL/Apo-2L-mediated killing of tumor cells was greatest with CpG-A ODN. Surprisingly, CD3⁺, CD14⁺, CD19⁺, and CD56⁺ PBMC expressed high levels of TRAIL/Apo-2L following CpG-A ODN stimulation. When isolated, the CD19⁺ PBMC (B cells) were able to kill tumor cells in a TRAIL/Apo-2L-dependent manner. As with CD14⁺ PBMC, CD19⁺ sorted B cells were capable of up-regulating TRAIL/Apo-2L expression when stimulated with IFN- alone. Interestingly, agonist anti-CD40 mAb further enhanced the IFN--induced TRAIL/Apo-2L expression on CD19⁺ B cells. These results are the first to demonstrate human B cell-mediated killing of tumor cells in a TRAIL/Apo-2L-dependent fashion.

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The JI 2004 173: 713-714. [Full Text]  

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