May, 2017
Mouse model of Epstein-Barr virus LMP1-and LMP2A-driven germinal center B-cell lymphoproliferative disease
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
- Volume
- 114
- Number
- 18
- First page
- 4751
- Last page
- 4756
- Language
- English
- Publishing type
- Research paper (scientific journal)
- DOI
- 10.1073/pnas.1701836114
- Publisher
- NATL ACAD SCIENCES
Epstein-Barr virus (EBV) is a major cause of immunosuppression-related B-cell lymphomas and Hodgkin lymphoma (HL). In these malignancies, EBV latent membrane protein 1 (LMP1) and LMP2A provide infected B cells with surrogate CD40 and B-cell receptor growth and survival signals. To gain insights into their synergistic in vivo roles in germinal center (GC) B cells, from which most EBV-driven lymphomas arise, we generated a mouse model with conditional GC B-cell LMP1 and LMP2A coexpression. LMP1 and LMP2A had limited effects in immunocompetent mice. However, upon T- and NK-cell depletion, LMP1/2A caused massive plasmablast outgrowth, organ damage, and death. RNA-sequencing analyses identified EBV oncoprotein effects on GC B-cell target genes, including up-regulation of multiple proinflammatory chemokines and master regulators of plasma cell differentiation. LMP1/2A coexpression also up-regulated key HL markers, including CD30 and mixed hematopoietic lineage markers. Collectively, our results highlight synergistic EBV membrane oncoprotein effects on GC B cells and provide a model for studies of their roles in immunosuppression-related lymphoproliferative diseases.
- Link information
- ID information
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- DOI : 10.1073/pnas.1701836114
- ISSN : 0027-8424
- Web of Science ID : WOS:000400358000056