期刊
JOURNAL OF CLINICAL INVESTIGATION
卷 121, 期 2, 页码 752-768出版社
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI44185
关键词
-
资金
- NIH [F30HL095287, T32 AI07496, T32 AI007046, R01CA088768, RC2 CA148038]
- University of Virginia Cancer Center [P30 CA44579]
Kaposi sarcoma-associated herpesvirus (KSHV; also known as HHV8) is the causative agent of two B cell tumors, multicentric Castleman disease (MCD) and primary effusion lymphoma (PEL). However, little is known about the nature of the specific B cell subtype(s) most susceptible to infection. Identifying these cells would provide direct insight into KSHV transmission and virus-induced transformation. To identify this subset and to determine whether infection alters its cellular phenotype, we exposed human tonsillar cells to KSHV and characterized infected cells using high-throughput multispectral imaging flow cytometry (MIFC). Stable expression of the virally encoded latency-associated nuclear antigen (LANA), a marker of latent KSHV infection, was observed predominantly in cells expressing the lambda light chain of the B cell receptor. These LANA(+) B cells proliferated and exhibited similarities to the cells characteristic of MCD (IgM lambda-expressing plasmablasts), including blasting morphology with elevated expression of Ki67, variable expression of CD27, and high levels of IgM and IL-6 receptor. Furthermore, the proportion of infected cells showing a blasting phenotype increased upon addition of exogenous IL-6. Our data lead us to propose that oral transmission of KSHV involves the latent infection of a subset of tonsillar IgM lambda-expressing B cells, which then proliferate as they acquire the plasmablast phenotype characteristic of MCD.
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