期刊
CELLULAR & MOLECULAR IMMUNOLOGY
卷 10, 期 4, 页码 360-372出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/cmi.2013.14
关键词
apoptosis; lymphoma B cells; NF-kappa B; Toll-like receptor
类别
资金
- National Institute of Health, USA [AI059617]
Toll-like receptor 9 (TLR9) recognizes microbial DNA containing unmethylated cytosyl guanosyl (CpG) sequences, induces innate immune responses, and facilitates antigen-specific adaptive immunity. Recent studies report that in addition to stimulating innate immunity, TLR9 ligands induce apoptosis of TLR9 expressing cancer cells. To understand the mechanism of TLR9-induced apoptosis, we compared the effects of CpG containing oligodeoxynucleotides (CpG ODN) on a mouse B-cell lymphoma line, CH27, with those on mouse splenic B cells. CpG ODN inhibited constitutive proliferation and induced apoptosis in the CH27 B-cell lymphoma line. In contrast, CpG ODN-treated primary Bcells were stimulated to proliferate and were rescued from spontaneous apoptosis. The induction of apoptosis required the ODNs to contain the CpG motif and the expression of TLR9 in lymphoma B cells. A decrease in Bcl-xl expression and an increase in Fas and Fas ligand expression accompanied lymphoma B-cell apoptosis. Treatment with the Fas ligand-neutralizing antibody inhibited CpG ODN-induced apoptosis. CpG ODN triggered a transient NF-kappa B activation in the B-cell lymphoma cell line, which constitutively expresses a high level of c-Myc, while CpG ODN induced sustained increases in NF-kappa B activation and c-Myc expression in primary B cells. Furthermore, an NF-kappa B inhibitor inhibited the proliferation of the CH27 B-cell lymphoma line. Our data suggest that the differential responses of lymphoma and primary B cells to CpG ODN are the result of differences in NF-kappa B activation. The impaired NF-kappa B activation in the CpG ODN-treated B-cell lymphoma cell line alters the balance between NF-kappa B and c-Myc, which induces Fas/Fas ligand-dependent apoptosis.
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