Standing out from the crowd: How to identify plasma cells

Tellier, Julie; Nutt, Stephen L.

doi:10.1002/eji.201747168

Cited by 56 publications

(63 citation statements)

References 29 publications

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“…The notion that M2 drives plasmablast differentiation is consistent with reports that M2.Stop virus persists in B lymphocytes which have not undergone class-switching (IgD + IgG2a - ) (28, 36). To determine whether M2 deletion from AID-expressing cells influences infection of plasmablasts in the spleen, we sorted CD138 + /CD38 lo cells from spleens of infected AID-Cre mice (37) ( Fig 7A ) and performed qPCR to quantify viral genomes. Interestingly, by this method of quantification, we observed a 4.5 cycle difference, indicative of a ca.…”

Section: Resultsmentioning

confidence: 99%

Deletion of Murine Gammaherpesvirus GeneM2in AID-Expressing B Cells Impairs Host Colonization and Viral Reactivation

Owens

Oldenburg

White

et al. 2020

Preprint

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1 Gammaherpesviruses (GHVs) are DNA tumor viruses that establish life-long, chronic 2 infections in lymphocytes of humans and other mammals. GHV infections are associated with 3 numerous cancers, especially in immune compromised hosts. While it is known that GHVs utilize 4 host germinal center (GC) B cell responses during latency establishment, an understanding of 5 how viral gene products function in specific B cell subsets to regulate this process is incomplete. 6 Using murine gammaherpesvirus 68 (MHV68) as a small-animal model to define mechanisms of 7 GHV pathogenesis in vivo, we generated a virus in which the M2 gene was flanked by loxP sites 8 (M2.loxP), enabling the use of Cre-lox technology to define M2 function in specific cell types in 9 infection and disease. The M2 gene encodes a protein that is highly expressed in GC B cells that 10 promotes plasma cell differentiation and viral reactivation. M2 was efficiently deleted in Cre-11 expressing cells, and the presence of loxP sites flanking M2 did not alter viral replication or latency 12 in mice that do not express Cre. In contrast, M2.loxP MHV68 exhibited a deficit in latency 13 establishment and reactivation that resembled M2-null virus, following intranasal (IN) infection of 14 mice that express Cre in all B cells (CD19-Cre). Nearly identical phenotypes were observed for 15 M2.loxP MHV68 in mice that express Cre in germinal center (GC) B cells (AID-Cre). However, 16 neither colonization of draining lymph nodes after IN infection nor the spleen after intraperitoneal 17(IP) infection required M2, although the reactivation defect was retained. Together, these data 18 confirm that M2 function is B cell-specific and demonstrate that M2 primarily functions in AID-19 expressing cells to facilitate MHV68 dissemination to distal latency reservoirs within the host and 20 reactivation from latency. Our study reveals that a viral latency gene functions within a distinct 21 subset of cells to facilitate host colonization. 22 131 M2 is required in CD19 + B cells for latency establishment and reactivation 132RT-PCR analyses suggest that a properly spliced M2 transcript capable of yielding the 133 functional M2 protein is only present in B cells (4, 23, 31). From this observation it is hypothesized 134 that M2 primarily functions in B cells to promote MHV68 latency and reactivation. To more 135 conclusively test this hypothesis, we infected mice that express Cre recombinase under control 136

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Section: Resultsmentioning

confidence: 99%

Deletion of Murine Gammaherpesvirus GeneM2in AID-Expressing B Cells Impairs Host Colonization and Viral Reactivation

Owens

Oldenburg

White

et al. 2020

Preprint

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“…Therefore, a second non-mutually exclusive model has been proposed wherein B cells differentiate into mostly IgG secreting LLPC, which are home to the bone marrow and can live for the lifetime of an organism (Figure 1) [37,44]. Although a specific phenotype that distinguishes SLPC from LLPC/MM cells has remained elusive, LLPC have increased expression of the transcription factors BLIMP1, XBP1, and IRF4 [45], but specific transcription factors necessary for PC development in certain inflammatory contexts are still being discovered as was the case for T-bet in a recent publication [46]. It has also been suggested that initial transcriptional programming through Zbtb20 may be critical in the induction of an LLPC [47].…”

Section: B Cell Biology and The Creation Of A Plasma Cellmentioning

confidence: 99%

Targeting Multiple Myeloma through the Biology of Long-Lived Plasma Cells

Utley

Lipchick

Lee

et al. 2020

Cancers

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Multiple myeloma (MM) is a hematological malignancy of terminally differentiated bone marrow (BM) resident B lymphocytes known as plasma cells (PC). PC that reside in the bone marrow include a distinct population of long-lived plasma cells (LLPC) that have the capacity to live for very long periods of time (decades in the human population). LLPC biology is critical for understanding MM disease induction and progression because MM shares many of the same extrinsic and intrinsic survival programs as LLPC. Extrinsic survival signals required for LLPC survival include soluble factors and cellular partners in the bone marrow microenvironment. Intrinsic programs that enhance cellular fidelity are also required for LLPC survival including increased autophagy, metabolic fitness, the unfolded protein response (UPR), and enhanced responsiveness to endoplasmic reticulum (ER) stress. Targeting LLPC cell survival mechanisms have led to standard of care treatments for MM including proteasome inhibition (Bortezomib), steroids (Dexamethasone), and immunomodulatory drugs (Lenalidomide). MM patients that relapse often do so by circumventing LLPC survival pathways targeted by treatment. Understanding the mechanisms by which LLPC are able to survive can allow us insight into the treatment of MM, which allows for the enhancement of therapeutic strategies in MM both at diagnosis and upon patient relapse.

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“…The segregated B and plasma cells differed based on their specific expression of CD19, CD20 and CD138 markers ( Fig. 2c), as CD19 + or/and CD20 + are uniquely expressed in B-cells whereas CD138 + (CD19 -CD20 -) is uniquely expressed in plasma cells 24 . Further, ScType accurately assigned various cell types in the human pancreas dataset, where it correctly labelled the subpopulation of macrophages that was incorrectly labelled as acinar cells in the original study 17 ( Supplementary Fig.…”

Section: Systematic Evaluation Of Sctype Across Multiple Scrna-seq Damentioning

confidence: 99%

Fully-automated and ultra-fast cell-type identification using specific marker combinations from single-cell transcriptomic data

Ianevski

Giri

Aittokallio

2019

Preprint

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Single-cell transcriptomics enables systematic charting of cellular composition of complex tissues.Identification of cell populations often relies on unsupervised clustering of cells based on the similarity of the scRNA-seq profiles, followed by manual annotation of cell clusters using established marker genes. However, manual selection of marker genes for cell-type annotation is a laborious and error-prone task since the selected markers must be specific both to the individual cell clusters and various cell types. Here, we developed a computational method, termed ScType, which enables data-driven selection of marker genes based solely on given scRNA-seq data.Using a compendium of 7 scRNA-seq datasets from various human and mouse tissues, we demonstrate how ScType enables unbiased, accurate and fully-automated single-cell type annotation by guaranteeing the specificity of marker genes both across cell clusters and cell types.The widely-applicable method is implemented as an interactive web-tool (https://sctype.fimm.fi), connected with comprehensive database of specific markers.

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Standing out from the crowd: How to identify plasma cells

Cited by 56 publications

References 29 publications

Deletion of Murine Gammaherpesvirus GeneM2in AID-Expressing B Cells Impairs Host Colonization and Viral Reactivation

Deletion of Murine Gammaherpesvirus GeneM2in AID-Expressing B Cells Impairs Host Colonization and Viral Reactivation

Targeting Multiple Myeloma through the Biology of Long-Lived Plasma Cells

Fully-automated and ultra-fast cell-type identification using specific marker combinations from single-cell transcriptomic data

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