Comparative Analysis of B-Cell Receptor Repertoires Induced by Live Yellow Fever Vaccine in Young and Middle-Age Donors

Davydov, Alexey N.; Obraztsova, Anna; Lebedin, Mikhail; Turchaninova, Maria A.; Staroverov, Dmitry B; Merzlyak, Ekaterina M.; Sharonov, George V; Кладова, О В; Shugay, Mikhail; Britanova, Olga V.; Chudakov, Dmitriy M.

doi:10.3389/fimmu.2018.02309

Cited by 27 publications

(20 citation statements)

References 73 publications

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“…Age-related BCR repertoire differences have been previously described, and this could be important as immune-mediated diseases often have different ages of onset. We confirmed this in both healthy controls and disease by incorporating age as a covariate in repertoire analyses, as in previous studies [41][42][43] .…”

Section: Accounting For Age In Bcr Analysissupporting

confidence: 88%

Analysis of the B cell receptor repertoire in six immune-mediated diseases

Bashford-Rogers

Bergamaschi

McKinney

et al. 2019

Nature

216

204

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B cells are important in the pathogenesis of many, and perhaps all, immune-mediated diseases (IMDs). Each B cell expresses a single B cell receptor (BCR) 1 , with the diverse range of BCRs expressed by an individual's total B cell population being termed the "BCR repertoire". Our understanding of the BCR repertoire in the context of IMDs is incomplete, and defining this could reveal new insights into pathogenesis and therapy. We therefore compared the BCR repertoire in systemic lupus erythematosus (SLE), ANCA-associated vasculitis (AAV), Crohn's disease (CD), Behçet's disease (BD), eosinophilic granulomatosis with polyangiitis (EGPA) and IgA vasculitis (IgAV), analysing BCR clonality, and immunoglobulin heavy chain gene (IGHV) and, in particular, isotype usage. An IgA-dominated increased clonality in SLE and CD, together with skewed IGHV gene usage in these and other diseases, suggested a microbial contribution to pathogenesis. Different immunosuppressive treatment had specific and distinct impacts on the repertoire; B cells persisting after rituximab were predominately isotype-switched and clonally expanded, the inverse of those persisting after mycophenolate mofetil. A comparative analysis of Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:

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Section: Accounting For Age In Bcr Analysissupporting

confidence: 88%

Analysis of the B cell receptor repertoire in six immune-mediated diseases

Bashford-Rogers

Bergamaschi

McKinney

et al. 2019

Nature

216

204

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“…Analysis of the immune repertoire of murine diffuse large B-cell lymphoma samples was performed as described in Turchaninova et al 63 . with minor modifications, which allowed us to introduce Illumina Nextera adapters and indexes during PCR 64 . Briefly, 700 ng RNA (extracted from whole tissue lysate) was transcribed into cDNA using a 5′ template switch oligo (TSO), which contains a unique molecular identifier.…”

Section: Methodsmentioning

confidence: 99%

PiggyBac transposon tools for recessive screening identify B-cell lymphoma drivers in mice

et al. 2019

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B-cell lymphoma (BCL) is the most common hematologic malignancy. While sequencing studies gave insights into BCL genetics, identification of non-mutated cancer genes remains challenging. Here, we describe PiggyBac transposon tools and mouse models for recessive screening and show their application to study clonal B-cell lymphomagenesis. In a genome-wide screen, we discover BCL genes related to diverse molecular processes, including signaling, transcriptional regulation, chromatin regulation, or RNA metabolism. Cross-species analyses show the efficiency of the screen to pinpoint human cancer drivers altered by non-genetic mechanisms, including clinically relevant genes dysregulated epigenetically, transcriptionally, or post-transcriptionally in human BCL. We also describe a CRISPR/Cas9-based in vivo platform for BCL functional genomics, and validate discovered genes, such as Rfx7 , a transcription factor, and Phip , a chromatin regulator, which suppress lymphomagenesis in mice. Our study gives comprehensive insights into the molecular landscapes of BCL and underlines the power of genome-scale screening to inform biology.

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“…However, the isolation of mAbs is low throughput and typically identifies only one or a few somatic variants from each Ab lineage, yielding limited information about the maturation of the response at the clonal level. In contrast, high-throughput Ab repertoire sequencing (Rep-seq) enables analyses of millions of B cells per sample, allowing definition of large numbers of clonally related sequences and more comprehensive understanding of Ab responses (Davydov et al, 2018; Galson et al, 2014; Georgiou et al, 2014; Jiang et al, 2013; Wiley et al, 2011; Yermanos et al, 2018). The use of Rep-seq is especially valuable if antigen-specific lineages can be identified in the data, as has been demonstrated for HIV-1 infection–induced Ab that undergo extensive affinity maturation (Bonsignori et al, 2016; Doria-Rose et al, 2014; Wu et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Extensive dissemination and intraclonal maturation of HIV Env vaccine-induced B cell responses

Phad

Pushparaj

Tran

et al. 2019

Journal of Experimental Medicine

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Well-ordered HIV-1 envelope glycoprotein (Env) trimers are prioritized for clinical evaluation, and there is a need for an improved understanding about how elicited B cell responses evolve following immunization. To accomplish this, we prime-boosted rhesus macaques with clade C NFL trimers and identified 180 unique Ab lineages from ∼1,000 single-sorted Env-specific memory B cells. We traced all lineages in high-throughput heavy chain (HC) repertoire (Rep-seq) data generated from multiple immune compartments and time points and expressed several as monoclonal Abs (mAbs). Our results revealed broad dissemination and high levels of somatic hypermutation (SHM) of most lineages, including tier 2 virus neutralizing lineages, following boosting. SHM was highest in the Ab complementarity determining regions (CDRs) but also surprisingly high in the framework regions (FRs), especially FR3. Our results demonstrate the capacity of the immune system to affinity-mature large numbers of Env-specific B cell lineages simultaneously, supporting the use of regimens consisting of repeated boosts to improve each Ab, even those belonging to less expanded lineages.

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Comparative Analysis of B-Cell Receptor Repertoires Induced by Live Yellow Fever Vaccine in Young and Middle-Age Donors

Cited by 27 publications

References 73 publications

Analysis of the B cell receptor repertoire in six immune-mediated diseases

Analysis of the B cell receptor repertoire in six immune-mediated diseases

PiggyBac transposon tools for recessive screening identify B-cell lymphoma drivers in mice

Extensive dissemination and intraclonal maturation of HIV Env vaccine-induced B cell responses

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