Abstract:

Objective To explore the molecular mechanisms of MALT lymphoma caused by BCL10 over-expression. Methods BCL10 transgenic (Tg ) mice were identified by BCL10 transgene specific PCR, and BCL10 protein expression were verified by Western Blot. MALT lymphoma precursor cellsmarginal zone(MZ) B cells expansion in BCL10 Tg mice were defined by histology methods and flow cytometry analysis, anti-apoptotic effects of separated MZ B cells were examined with Annexin V-FITC / PI staining. Results The BCL10 Tg/+ mice used in the experiment were verified by transgene specific PCR. Protein expression of transgene is almost at the same level as endogenous BCL10, which means, in Tg/+ mice, BCL10 protein has doubled than that in nontransgenic WT mice. By histology, we found B cells expansion in Tg/+ mice which look like MZ B cells morphologically. By verification with CD21,CD23 staining followed by flow cytometry analysis, it is proven those expanded B cells are CD21high/CD23low MZ B cells. To investigate the mechanisms causing the MZ B cells expansion, we separate the MZ B cells from both Tg/+ and WT control mice by cell sorting with CD43, CD23 double staining. About 30% separated MZ B cells from Tg/+ mice can survive at least up to one week in RPMI-1640 containing 5% FBS, but those from WT mice almost all died at day 3（P＜0.01）, this result means overexpression of BCL10 in MZ B cells causes anti-apoptotic effects to those cells. We studied pathways of antiapoptotic that BCL10 might be involved by inducing apoptosis with anti-IgM, BCL10 over-expression protect antiIgM caused cell apoptosis. Conclusion Over-expression of BCL10 causes expansion of MZ B cells which have anti-apoptotic property. This property is involved antigen receptor pathway. These results may partially answer the molecular mechanisms of MALT lymphoma with t(1; 14) (p22; q32) chromosome translocation.

Key words: BCL10 transgenic mice, MALT lymphoma, marginal zone B cell, anti apoptosis