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VR09 细胞系：一种 EBV 阳性淋巴母细胞系，具有激活 B 细胞型弥漫性大 B 细胞淋巴瘤的体内特征。

VR09 cell line: an EBV-positive lymphoblastoid cell line with in vivo characteristics of diffuse large B cell lymphoma of activated B-cell type.

机构信息

Stem Cell Research Laboratory, Section of Hematology, Department of Medicine, University of Verona, Verona, Italy.

出版信息

PLoS One. 2012;7(12):e52811. doi: 10.1371/journal.pone.0052811. Epub 2012 Dec 21.

DOI:10.1371/journal.pone.0052811
PMID:23285191
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3528718/
Abstract

BACKGROUND

small B-cell neoplasms can show plasmacytic differentiation and may potentially progress to aggressive lymphoma (DLBCL). Epstein-Barr virus (EBV) infection may cause the transformation of malignant cells in vitro.

DESIGN AND METHOD

we established VR09 cell line with plasmacytic differentiation, obtained from a case of atypical, non-CLL B-cell chronic lymphoproliferative disease with plasmacytic features. We used flow cytometry, immunohistochemistry, polymerase chain reaction, cytogenetic analysis and florescence in situ hybridization in the attempt at thoroughly characterizing the cell line. We showed VR09 tumorigenic potential in vivo, leading to the development of activated DLBCL with plasmacytic features.

RESULTS

VR09 cells displayed plasmacytic appearance 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+ cyclin D1- Ki67 80% IgM+ IgD+ MUM1+ MNDA+ CD10- CD22+ CD23+ CD43+ K+, λ- Bcl2+ Bcl6-) and they presented episomal EBV genome, chromosome 12 trisomy, lack of c-MYC rearrangement and Myd88 gene mutation, presence of somatic hypermutation in the VH region, and wild-type p53.

CONCLUSION

This new EBV-positive cell line may be useful to further characterize in vivo activated DLBCL with plasmacytic features.

摘要

背景

小 B 细胞肿瘤可表现为浆细胞分化，并可能潜在进展为侵袭性淋巴瘤（DLBCL）。EB 病毒（EBV）感染可能导致体外恶性细胞的转化。

设计与方法

我们建立了一个具有浆细胞分化特征的 VR09 细胞系，该细胞系源自一例具有浆细胞特征的非 CLL B 细胞慢性淋巴增生性疾病的不典型病例。我们使用流式细胞术、免疫组织化学、聚合酶链反应、细胞遗传学分析和荧光原位杂交来试图对该细胞系进行全面表征。我们证明了 VR09 细胞在体内的致瘤潜能，导致具有浆细胞特征的激活型 DLBCL 的发展。

结果

当将 VR09 细胞皮下接种于免疫缺陷 Rag2(-/-) γ-链(-/-)小鼠中时，它们呈现出浆细胞样外观，并生长为球形肿瘤。VR09 细胞系和肿瘤显示出 B 细胞成熟激活阶段的表型，具有分泌分化（CD19+ CD20+ CD79a+ CD79b+/- CD138+ cyclin D1- Ki67 80% IgM+ IgD+ MUM1+ MNDA+ CD10- CD22+ CD23+ CD43+ K+，λ- Bcl2+ Bcl6-），并呈现出游离 EBV 基因组、12 号染色体三体、c-MYC 重排缺失和 Myd88 基因突变、VH 区体细胞高频突变以及野生型 p53。

结论

这种新的 EBV 阳性细胞系可能有助于进一步表征体内具有浆细胞特征的激活型 DLBCL。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe34/3528718/95a9ac913797/pone.0052811.g006.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe34/3528718/b51a45f91c20/pone.0052811.g004.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe34/3528718/95a9ac913797/pone.0052811.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe34/3528718/0263281cce2e/pone.0052811.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe34/3528718/79d91e1fd139/pone.0052811.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe34/3528718/5b15906c492b/pone.0052811.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe34/3528718/b51a45f91c20/pone.0052811.g004.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe34/3528718/95a9ac913797/pone.0052811.g006.jpg

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