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KSHV infects a subset of human tonsillar B cells, driving proliferation and plasmablast differentiation
Lynn M. Hassman, … , Thomas J. Ellison, Dean H. Kedes
Lynn M. Hassman, … , Thomas J. Ellison, Dean H. Kedes
Published January 18, 2011
Citation Information: J Clin Invest. 2011;121(2):752-768. https://doi.org/10.1172/JCI44185.
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Research Article

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

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

Authors

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

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Figure 3

LANA expression is evident primarily in λ tonsillar B cells.

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LANA expression is evident primarily in λ tonsillar B cells.
Tonsil cell...
Tonsil cells from 8 donors were exposed to KSHV and analyzed by MIFC at 60–84 hpi to determine susceptible subsets. (A) Representative images of cells labeled with antibodies to LANA, κ, and λ. (B) Representative scatter plot of κ versus λ staining of tonsillar cells. Gates were drawn to include all B cells (λ+ + κ+) versus non-B cells (λ– κ–). (C) Left panel: Percentage of non-B cells (λ– κ–) or B cells (λ+ + κ+) expressing LANA dots from individual donors represented by individual symbols. Right panel: Percentage of κ or λ B cells expressing LANA dots from individual donors represented by symbols that correspond to those in the left panel. Horizontal bars represent the mean value for all donors.

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