B cell lymphomas originate from specialized microenvironment, the germinal center (GC). The GC is composed exclusively of B cells and Follicular Dendritic Cells (FDC). The GC stromal cells, FDC, provide a nurturing environment for survival and growth of lymphoma cells. We established a lymphoma model using a lymphoma cell line and an FDC cell line. Lymphoma cell line L3055 requires FDC or FDC cell line to grow in vitro and to form tumor in vivo. However, L3055 cells from tumors in mice become less FDC-independent. This result suggests that some remarkable genetic changes have occurred in L3055 cells in the course of tumor formation. This phenomenon is analogous to the clinic situation where indolent Follicular Lymphomas (FL) undergo malignant transformation into Diffuse Large B Cell Lymphomas (DLBCL).
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Hence we examined differential gene profiles between FDC-dependent and FDC-independent L3055 cells to identify the genes activated for malignant transformation using microarray technique. 17 gene were upregulated in FDC-independent L3055 cells and 20 genes upregulated in FDC-dependent L3055 cells. We confirmed the microarray data at the mRNA level and at the protein level. Among these genes, difference in the expression of CD9 and Annexin2 is remarkable. CD9 was highly expressed in HK-dependent clone but not expressed in HK-independent clone. At the same time annexin2 is more expressed in HK-independent clone then HK-dependent clone. Therefore, we will investigate their functional roles in malignant transformation.
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