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

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

doi:10.1172/jci44185

Cited by 102 publications

(125 citation statements)

References 80 publications

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“…Naive B cells, memory B cells, and ASCs were characterized as CD19 Differential expression between plasmablasts and plasma cells was used to investigate ASC subsets. Unlike plasmablasts and memory B cells, plasma cells express very low level of MHC class II (HLA-DR) (20)(21)(22) and also express CD138 (a well-known marker for plasma cell) (18,(23)(24)(25).…”

Section: Flow Cytometric Analysis Of B Cell Subsetsmentioning

confidence: 99%

Human Memory B Cells in Healthy Gingiva, Gingivitis, and Periodontitis

Mahanonda

Champaiboon

Subbalekha

et al. 2016

The Journal of Immunology

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The presence of inflammatory infiltrates with B cells, specifically plasma cells, is the hallmark of periodontitis lesions. The composition of these infiltrates in various stages of homeostasis and disease development is not well documented. Human tissue biopsies from sites with gingival health (n = 29), gingivitis (n = 8), and periodontitis (n = 21) as well as gingival tissue after treated periodontitis (n = 6) were obtained and analyzed for their composition of B cell subsets. Ag specificity, Ig secretion, and expression of receptor activator of NF-κB ligand and granzyme B were performed. Although most of the B cell subsets in healthy gingiva and gingivitis tissues were CD19+CD27+CD38− memory B cells, the major B cell component in periodontitis was CD19+CD27+CD38+CD138+HLA-DRlow plasma cells, not plasmablasts. Plasma cell aggregates were observed at the base of the periodontal pocket and scattered throughout the gingiva, especially apically toward the advancing front of the lesion. High expression of CXCL12, a proliferation-inducing ligand, B cell–activating factor, IL-10, IL-6, and IL-21 molecules involved in local B cell responses was detected in both gingivitis and periodontitis tissues. Periodontitis tissue plasma cells mainly secreted IgG specific to periodontal pathogens and also expressed receptor activator of NF-κB ligand, a bone resorption cytokine. Memory B cells resided in the connective tissue subjacent to the junctional epithelium in healthy gingiva. This suggested a role of memory B cells in maintaining periodontal homeostasis.

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Section: Flow Cytometric Analysis Of B Cell Subsetsmentioning

confidence: 99%

Human Memory B Cells in Healthy Gingiva, Gingivitis, and Periodontitis

Mahanonda

Champaiboon

Subbalekha

et al. 2016

The Journal of Immunology

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“…MIFC has become an established technique for the highthroughput analysis of protein expression and localization in heterogeneous populations of cells (Adang et al 2006;Basiji et al 2007;Hassman et al 2011). We report that use of MIFC can be expanded to include the analysis of RNA as well as protein molecules in the same cell population.…”

Section: Discussionmentioning

confidence: 99%

“…Single-plane images were analyzed, as opposed to images obtained from an extended depth of field (EDF) (as described by Ortyn et al 2007;Hassman et al 2011), because the use of EDF is best suited for analysis of cells with limited numbers of punctate foci each with distinct x-and y-coordinates. If, instead, signals in each cell are either too numerous such that they share x-and y-coordinates and are separated only in the z-axis (depth of cell) and/or are dimensionally large, EDF compression results in the merging of signals.…”

Section: Data Collection and Analysismentioning

confidence: 99%

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Tracking expression and subcellular localization of RNA and protein species using high-throughput single cell imaging flow cytometry

Borah¹,

Nichols²,

Hassman³

et al. 2012

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We report a high-throughput application of multispectral imaging flow cytometry (MIFC) for analyzing the expression and localization of both RNA and protein molecules in a heterogeneous population of cells. The approach was developed using polyadenylated nuclear (PAN) RNA, an abundant, noncoding RNA expressed by Kaposi's sarcoma-associated herpesvirus (KSHV) during the lytic phase of infection. High levels of PAN RNA are, in part, dependent on its interaction with poly(A)-binding protein C1 (PABPC1), which relocalizes from the cytoplasm to the nucleus of lytically infected cells. We quantitatively tracked the cytoplasmic to nuclear translocation of PABPC1 and examined how this translocation relates to the expression and localization of viral RNA and protein molecules in KSHV-infected cells. This high-throughput approach will be useful for other systems in which changes in subcellular localization of RNA and protein molecules need to be monitored simultaneously.

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“…Kaposi's sarcomaassociated herpesvirus (KSHV) is a γ2 herpesvirus and the causative agent of Kaposi's sarcoma (KS), as well as two B-cell malignancies, multicentric Castleman's disease (MCD) (297) and primary effusion lymphoma (PEL) (reviewed in (46)). KSHV infects endothelial cells, but can also establish latency and replicate in T and B lymphocytes (123,206,220,221,257). …”

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confidence: 99%

Role of RRV ORF52 in Virion Maturation

Anderson¹

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Rhesus monkey rhadinovirus (RRV) is a close relative of the human pathogen, Kaposi's Sarcoma-Associated Herpesvirus (KSHV). Primary infection with KSHV in culture is highly inefficient and it predominantly adopts a latent phenotype, expressing only a minimal number of viral genes and producing no progeny virions. This contrasts with RRV in culture, which replicates to high viral titer and produces abundant progeny virions, making it a useful model to study gammaherpesvirus lytic replication, virion structure, and the potential roles of tegument proteins in the biology of gammaherpesviruses. Initial work in our laboratory determined that the RRV virion was composed of 33 virally encoded proteins. Of these, 17 are tegument proteins, five of which are unique to the gammaherpesvirus subfamily. ORF52 is one of these five gammaherpesvirus specific tegument proteins and is the focus of this dissertation. This protein is highly abundant within the virion (approximately 1000 copies per particle) and it is closely associated with the capsid. Our results describe a critical role for ORF52 in the cytoplasmic-based later stages of virion morphogenesis. Without ORF52, capsids fail to undergo tegumentation, which is necessary for final envelopment and production of fully infectious virions. In a later section of this dissertation, we also describe preliminary data proposing that ORF52 may play a direct or indirect role in virion transport through interaction with cellular microtubules.iii ACKNOWLEDGEMENTS I grew up in a small, blue-collar, southern Illinois town where most people stay local and focus on getting by day-to-day, not on things like big cities and advanced degrees. I didn't even know what "graduate school" was until several years into my undergraduate education in Chicago, which, by the way, took me 9 years to complete because I worked full-time and went to school off-and-on and part-time when time and money permitted. The reason I share this is because I didn't get here alone, I didn't even know where "here" was and if I'm honest, I don't think I ever really believed I would earn a PhD, because where I'm from, things like that just don't happen to people like me. There truly are so many people I am honored to thank for helping, and supporting, me at various points in this long, wonderful, horrible, amazing, and trying journey that has been the last 10 years of my life, 7 of those at UVa.

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

Cited by 102 publications

References 80 publications

Human Memory B Cells in Healthy Gingiva, Gingivitis, and Periodontitis

Human Memory B Cells in Healthy Gingiva, Gingivitis, and Periodontitis

Tracking expression and subcellular localization of RNA and protein species using high-throughput single cell imaging flow cytometry

Role of RRV ORF52 in Virion Maturation

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