Translocation of Helicobacter pylori CagA into Human B lymphocytes, the origin of mucosa-associated lymphoid tissue lymphoma.
Infection by cagA-positive Helicobacter pylori (H. pylori) is strongly associated with gastric carcinomas and gastric mucosa-associated lymphoid tissue (MALT) lymphomas. H. pylori translocates the bacterial protein CagA into gastric epithelial cells, and the translocated CagA deregulates intracellular signaling pathways and thereby initiates pathogenesis. This in turn raised the possibility that H. pylori is associated with the development of MALT lymphomas during persistent infection by direct interaction with B lymphocytes. In this work, we showed that CagA can be directly translocated into human B lymphoid cells by H. pylori, and the translocated CagA undergoes tyrosine phosphorylation and binds to intracellular SH-2. Meanwhile, the translocated CagA induces activation of extracellular signal-regulated kinase and p38 mitogen-activated protein kinase in human B lymphoid cells, and upregulates the expressions of Bcl-2 and Bcl-X(L), which prevents apoptosis. These results provide the first direct evidence for the role of CagA as a bacterium-derived oncoprotein that acts in human B cells, and further implies that CagA is directly delivered into B cells by H. pylori and is associated with the development of MALT lymphomas.
Lin
Wei-Cheng
WC
Graduate Institute of Immunology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Tsai
Hwei-Fang
HF
Kuo
Sung-Hsin
SH
Wu
Ming-Shiang
MS
Lin
Chung-Wu
CW
Hsu
Ping-I
PI
Cheng
Ann-Lii
AL
Hsu
Ping-Ning
PN
D000942:Antigens, Bacterial / Q000378:metabolism*; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D001426:Bacterial Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D004789:Enzyme Activation; D016481:Helicobacter Infections / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016480:Helicobacter pylori / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D016393:Lymphoma, B-Cell / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D018442:Lymphoma, B-Cell, Marginal Zone / Q000276:immunology / Q000378:metabolism / Q000382:microbiology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015854:Up-Regulation; D051020:bcl-X Protein / Q000378:metabolism
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; C080866:cagA protein, Helicobacter pylori; D020928:Mitogen-Activated Protein Kinases