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 devel op from chronic infection with Helicobacter sp, in the mouse model. The mec hanisms 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 exp ression 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 o f gastric MALT lymphoma associated with Helicobacter infection using the BA LB/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), i nvestigating the in vivo distribution of Bcl-X-L in B cells/B-lymphoma cell s using immunohistochemical analysis. In vitro cultivation of B cells/B-lym phoma cells was employed to perform RT-PCR analysis of Bcl-X-L mRNA express ion 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 stimulat ion 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 ly mphoma by providing cell-survival signals and by triggering the acquisition of MALT. (C) 2001 Wiley-Liss, Inc.