Helicobacter pylori Activates NF-κB via the Alternative Pathway in B Lymphocytes

• Published in: Journal of Immunology Vol. 175; no. 11; pp. 7162 - 7169
• Main Authors: Ohmae, Tomoya, Hirata, Yoshihiro, Maeda, Shin, Shibata, Wataru, Yanai, Ayako, Ogura, Keiji, Yoshida, Haruhiko, Kawabe, Takao, Omata, Masao
• Format: Journal Article
• Language: English
• Published: 01-12-2005
• Subjects: Helicobacter pylori
• ISSN: 0022-1767; 1550-6606; 1365-2567
• DOI: 10.4049/jimmunol.175.11.7162

Abstract
Helicobacter pylori causes various gastroduodenal diseases including gastric MALT lymphoma, but the mechanism underlying H. pylori-induced carcinogenesis is not known. The alternative pathway for NF-κB activation, which involves the processing of NF-κB2/p100 to p52, has been implicated in lymphocyte survival, attenuated apoptosis, and secondary lymphoid tissue development. In this study, we investigated H. pylori-induced activation of NF-κB through the alternative pathway in B lymphocytes. In immunoblot and EMSA, H. pylori induced NF-κB2/p100 processing to p52 and subsequent nuclear accumulation in IM-9 (human B cell line) cells and human peripheral blood B cells, but not in AGS (human gastric cancer cell line) cells. The activation of the alternative pathway was LPS-dependent but not cag pathogenicity island-dependent. Alternative pathway activation by H. pylori was associated with attenuated apoptosis. The expression levels of B lymphocyte chemoattractant, EBI-1 ligand chemokine, and stromal cell-derived factor-1α mRNAs were up-regulated in cocultured human B cells and in infected human gastric mucosa. In the infected mucosa, NF-κB2/p100 and p52 were detected immunohistochemically in the cytoplasm and nuclear compartments of lymphocytes, but not in epithelial cells. In summary, H. pylori activates the alternative NF-κB pathway in B lymphocytes. The effects on chemokine production and antiapoptosis mediated by H. pylori-induced processing of NF-κB2/p100 to p52 may drive lymphocytes to acquire malignant potential.