Paediatrics (RCH) - Research Publications

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    Helicobacter-induced expression of Bcl-XL in B lymphocytes in the mouse model:: A possible step in the development of gastric mucosa-associated lymphoid tissue (MALT) lymphoma
    Morgner, A ; Sutton, P ; O'Rourke, JL ; Enno, A ; Dixon, MF ; Lee, A (WILEY-LISS, 2001-06-01)
    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.