KSHV infects a subset of human tonsillar B cells, driving proliferation and plasmablast differentiation.
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.
Myles H. Thaler Center for AIDS and Human Retrovirus Research, University of Virginia Health Systems, Charlottesville, Virginia, USA.
Lynn M
LM
Hassman
Thomas J
TJ
Ellison
Dean H
DH
Kedes
D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D005871:Castleman Disease / Q000276:immunology / Q000473:pathology / Q000821:virology; D002454:Cell Differentiation / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D018562:Disease Transmission, Infectious; D016679:Genome, Viral; D019288:Herpesvirus 8, Human / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D006801:Humans; D054685:Lymphoma, Primary Effusion / Q000276:immunology / Q000473:pathology / Q000821:virology; D009687:Nuclear Proteins / Q000276:immunology; D014066:Palatine Tonsil / Q000166:cytology* / Q000276:immunology; D010950:Plasma Cells / Q000166:cytology / Q000276:immunology*
D000956:Antigens, Viral; D009687:Nuclear Proteins; C109540:latency-associated nuclear antigen
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