Changes in Tonsil B Cell Phenotypes and EBV Receptor Expression in Children Under 5‐Years‐Old

Wohlford, Eric M.; Baresel, Paul C.; Wilmore, Joel R.; Mortelliti, Anthony J.; Coleman, Carrie B.; Rochford, Rosemary

doi:10.1002/cyto.b.21589

Cited by 9 publications

(7 citation statements)

References 43 publications

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“…2H), and subsequent imaging confirmed spatially restricted expression of CD21 ( Fig. 2B), consistent with the absence of a follicular dendritic cell network in the sectioned plane of one follicle (21). We conclude that Pick-Seq can uncover spatially restricted gene expression patterns from FFPE tissue and these patterns can be confirmed by imaging.…”

Section: Differentially Expressed Genes (Degs) Between the T-cell Zonsupporting

confidence: 70%

Micro-region transcriptomics of fixed human tissue using Pick-Seq

Maliga

Nirmal

Ericson

et al. 2021

Preprint

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Spatial transcriptomics and multiplexed imaging are complementary methods for studying tissue biology and disease. Recently developed spatial transcriptomic methods use fresh-frozen specimens but most diagnostic specimens, clinical trials, and tissue archives rely on formaldehyde-fixed tissue. Here we describe the Pick-Seq method for deep spatial transcriptional profiling of fixed tissue. Pick-Seq is a form of micro-region sequencing in which small regions of tissue, containing 5-20 cells, are mechanically isolated on a microscope and then sequenced. We demonstrate the use of Pick-Seq with several different fixed and frozen human specimens. Application of Pick-Seq to a human melanoma with complex histology reveals significant differences in transcriptional programs associated with tumor invasion, proliferation, and immuno-editing. Parallel imaging confirms changes in immuno-phenotypes and cancer cell states. This work demonstrates the ability of Pick-Seq to generate deep spatial transcriptomic data from fixed and archival tissue with multiplexed imaging in parallel.

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Section: Differentially Expressed Genes (Degs) Between the T-cell Zonsupporting

confidence: 70%

Micro-region transcriptomics of fixed human tissue using Pick-Seq

Maliga

Nirmal

Ericson

et al. 2021

Preprint

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“…qRT-PCR were performed with the SYBR Green PCR mix (SensiFast hi ROX syber green BIO820025) for different interest targets (supplemental table 3) or with Taqman PCR mix (SensiFast Probe Hi-Rox kit BIO820025) and cMYC probe (4331182 Hs00905030_m1, thermofisher). Normal centroblasts were sorted as described 23 from tonsils.…”

Section: Methodsmentioning

confidence: 99%

Increased frequencies of IgH locus suicide recombination points on Chronic Lymphocytic Leukemia with low rate of AID related somatic mutations, cMYC overexpression and short telomeres

Jamal

Parquet

Boutouil

et al. 2022

Preprint

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In normal activated B-cells, Activation Induced-cytidine deaminase (AID) is absolutely required for immunoglobulin (Ig) class switch recombination (CSR) and IGHV somatic hypermutation (SHM). AID is also implicated in the Locus Suicide Recombination (LSR) of the Ig heavy (IgH) locus, resulting in the deletion of the IgH constant part. Chronic lymphocytic leukemia (CLL) is an indolent non-Hodgkin B-cell lymphoma characterized by tumor CLL B-cells that weakly express a B cell receptor (BCR) on their surface. The great majority of CLL tumor B-cells are non class-switched. Searching for abnormalities of IgH locus recombination in CLL, we investigated CSR and LSR in samples from CLL patients (N=47) with high blood tumor cell infiltration (>98%) and in healthy volunteers (HV) as controls (N=9). LSR was detectable at comparable levels in both HV and CLL groups. CSR counts were decreased in CLL samples as expected. As distribution of LSR counts was bimodal, we separated CLL patients in two groups so called LSRHigh and LSRLow. LSRHigh CLLs exhibited very weak AID expression and low mutation rate of IgHV region and of the AID off-target PIM1 gene. LSR junction diversity, evaluated using the Shannon index, was increased in LSRHigh CLLs suggesting that LSR was on-going in these cells. Also, shorter telomeres were observed in LSRHigh CLLs suggesting an increased number of past mitosis. Consistently, increased levels of cMYC expression were detected in LSRHigh CLLs and treatment free survival of these cases was markedly decreased. We hypothesized that LSR in LSRHigh CLLs is AID independent and could be due to DNA lesion and inaccurate DSB repair within the IgH locus which could be accessible to recombination machinery due to increased IgH locus transcription. Altogether, our results indicate the accessibility of IgH locus and the proliferation increase LSR rate in LSRHigh CLLs could be related to cMYC resulting in shorter treatment free survival of patients and point on an AID independent mechanism of IgH recombination.

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“…During the initial stages, EBV spreads through the saliva and affects the tonsils. The naïve B cells and the follicular dendritic cells in the tonsils bind with the surface glycoprotein of the virus through the complement receptor CD21 [ 14 ]. This further activates the B cells, and the virus catalyzes the differentiation of the normal cellular pathway of the B cell through the expression of the viral latent proteins: namely, Epstein–Barr nuclear antigens (EBNA) and latent membrane proteins (LMP).…”

Section: Infection Cyclementioning

confidence: 99%

Molecular Genetics in Epstein–Barr Virus-Associated Malignancies

Umakanthan

Bukelo

2021

Life

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Global genomic studies have detected the role of genomic alterations in the pathogenesis of Epstein–Barr virus (EBV)-associated tumors. EBV oncoproteins cause a vital shift of EBV from an infectious virus to an oncogenic form during the latent and lytic phase within the lymphoid B cells and epithelial cells. This epigenetic alteration modulates the virus and host genomes and inactivates and disrupts numerous tumor suppressors and signaling pathways. Genomic profiling has played the main role in identifying EBV cancer pathogenesis and its related targeted therapies. This article reviews the role of genetic changes in EBV-associated lymphomas and carcinomas. This includes the prolific molecular genesis, key diagnostic tools, and target-specific drugs that have been in recent clinical use.

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Changes in Tonsil B Cell Phenotypes and EBV Receptor Expression in Children Under 5‐Years‐Old

Cited by 9 publications

References 43 publications

Micro-region transcriptomics of fixed human tissue using Pick-Seq

Micro-region transcriptomics of fixed human tissue using Pick-Seq

Increased frequencies of IgH locus suicide recombination points on Chronic Lymphocytic Leukemia with low rate of AID related somatic mutations, cMYC overexpression and short telomeres

Molecular Genetics in Epstein–Barr Virus-Associated Malignancies

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