Helicobacter-induced expression of Bcl-X(L) in B lymphocytes in the mouse model: a possible step in the development of gastric mucosa-associated lymphoid tissue (MALT) lymphoma.
Primary gastric mucosa-associated lymphoid tissue (MALT) lymphoma may develop from chronic infection with Helicobacter sp. in the mouse model. The mechanisms of pathogenesis remain unclear. Regulation of B-cell proliferation and death are important features to investigate. Proteins encoded by bcl-2 family genes, e.g., Bcl-X(L), regulate apoptosis; and alterations in the expression of these genes can contribute to the development of cancer. Our aim was to determine the role of Bcl-X(L) in B lymphocytes in the development of gastric MALT lymphoma associated with Helicobacter infection using the BALB/c mouse model. We analyzed 37 animals with Helicobacter-associated MALT (n = 25), low-grade MALT lymphoma (n = 10) and high-grade lymphoma (n = 2), investigating the in vivo distribution of Bcl-X(L) in B cells/B-lymphoma cells using immunohistochemical analysis. In vitro cultivation of B cells/B-lymphoma cells was employed to perform RT-PCR analysis of Bcl-X(L) mRNA expression after cell stimulation with Helicobacter antigen. We found significant Bcl-X(L) protein expression in B lymphocytes within MALT and low-grade MALT lymphoma, whereas there was no and minimal expression, respectively, of Bcl-X(L) in the 2 high-grade MALT lymphoma cases. Expression of bcl-X(L) mRNA in B lymphocytes was up-regulated in vitro upon Helicobacter-antigen stimulation and associated with prolonged cell survival. These findings support the hypothesis that Bcl-X(L) plays a role in the pathogenesis of B-cell MALT lymphoma by providing cell-survival signals and by triggering the acquisition of MALT.
Morgner
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Medical Department I, Technical University of Dresden, Fetscherstrasse 74, 01307 Dresden, Germany. andrea.morgner@t-online.de
Sutton
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P
O'Rourke
J L
JL
Enno
A
A
Dixon
M F
MF
Lee
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D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism*; D002455:Cell Division; D005260:Female; D016481:Helicobacter Infections / Q000150:complications* / Q000378:metabolism; D007150:Immunohistochemistry; D018442:Lymphoma, B-Cell, Marginal Zone / Q000209:etiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D013274:Stomach Neoplasms / Q000209:etiology*; D051020:bcl-X Protein
C494812:Bcl2l1 protein, mouse; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051020:bcl-X Protein