In vitro and in vivo model of ebv-positive activated diffuse large b cell lymphoma with plasmacytic differentiation

Background: B-cell lymphoproliferative diseases can show plasmacytic differentiation and may potentially progress to diffuse large B cell lymphoma (DLBCL). Epstein-Barr virus infection may cause the transformation of malignant cells in vitro. Design and Method: we established VR09 cell line, a DLBCL cell line with plasmacytic differentiation, obtained from a case of atypical B-cell chronic lymphoproliferative disease with plasmacytic features. We used flow cytometry, immunohistochemistry, polymerase chain reaction, cytogenetic analysis and florescence in situ hybridization to characterize this cell line. We also assessed whether VR09 has tumorigenic potential in vivo. Results: cells in suspension revealed plasmacytic features and grew as spherical tumors when inoculated subcutaneously into immunodeficient Rag2-/- γ-chain-/- mice. VR09 cell line and tumors displayed the phenotype of activated stage of B cell maturation, with secretory differentiation (CD19+ CD20+ CD79a+ CD79b+/- CD138+/- cycline D1- Ki67 80% IgM+ IgD+ MUM1+ MDNA+ CD10- CD22+ CD23+ CD43+ K+, λ- Bcl2+ Bcl6-); in addition they displayed episomal EBV genome, chromosome 12 trisomy, absence of c-MYC rearrangement, presence of somatic hypermutation in the VH region, mutations of Card 11 and CD79B genes, and wild-type p53. Conclusion: This new EBV-positive cell line may be useful to further characterize activated DLBCL with plasmacytic features.