期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 114, 期 18, 页码 4751-4756出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1701836114
关键词
Epstein-Barr virus; LMP1; LMP2A; posttransplant lymphoproliferative disorder; plasmablast
资金
- Japan Society for the Promotion of Science [JP16K14650]
- Japan Agency for Medical Research and Development [16mk01010480302]
- Burroughs Wellcome Fund Career Award in Medical Sciences
- Leukemia & Lymphoma Society [5444-16]
- National Cancer Institute [RO1 CA085180]
- National Institute of Allergy and Infectious Disease [AI123420]
- Grants-in-Aid for Scientific Research [16K14650, 25461157, 16K09537] Funding Source: KAKEN
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据