KSHV infects a subset of human tonsillar B cells, driving proliferation and plasmablast differentiation

Lynn M. Hassman, Thomas J. Ellison, Dean H. Kedes

Research output: Contribution to journalArticlepeer-review

76 Scopus citations

Abstract

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 λ light chain of the B cell receptor. These LANA+ B cells proliferated and exhibited similarities to the cells characteristic of MCD (IgMλ-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 IgMλ-expressing B cells, which then proliferate as they acquire the plasmablast phenotype characteristic of MCD.

Original languageEnglish
Pages (from-to)752-768
Number of pages17
JournalJournal of Clinical Investigation
Volume121
Issue number2
DOIs
StatePublished - Feb 1 2011

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