Comprehensive analyses of B-cell compartments across the human body reveal novel subsets and a gut-resident memory phenotype

Weisel, Nadine M.; Weisel, Florian; Farber, Donna L.; Borghesi, Lisa; Shen, Yufeng; Wei-hua, MA; Prak, Eline Luning; Shlomchik, Mark J.

doi:10.1182/blood.2019002782

Cited by 88 publications

(77 citation statements)

References 46 publications

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“…Whole transcriptome profiling by RNA sequencing (RNA-seq) generates read counts of all the transcripts within a population and differential gene expression analysis can reveal signatures that define specific subsets (Stark et al, 2019). RNA-seq has been used to define T RM as a distinct subset in mice and humans (Kumar et al, 2017;Mackay and Kallies, 2017;Mackay et al, 2016) and distinct features of human B cell subsets in blood and tissues (Weisel et al, 2020). Applying whole transcriptome profiling to single cells (scRNA-seq) enables identification and stratification of cell subsets based on differential gene expression and can lead to de novo discovery of new cell types and cell states, as well as tissue-specific adaptations of cell types within and across tissues (Figure 2).…”

Section: Methods and Computational Approaches In Systems Immunologymentioning

confidence: 99%

The Whole Body as the System in Systems Immunology

Poon

Farber

2020

iScience

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Summary The human immune system is comprised of a diverse and interactive network of specialized cells localized in diverse tissues throughout the body, where they mediate protection against pathogens and environmental insults while maintaining tissue homeostasis. Although much of our understanding of human immunology has derived from studies of peripheral blood, recent work utilizing human tissue resources and innovative computational methods have employed a whole-body, systems-based approach, revealing tremendous complexity and heterogeneity of the immune system within individuals and across the population. In this review, we discuss how tissue localization, developmental and age-associated changes, and conditions of health and disease shape the immune response, as well as how improved understanding of interindividual and tissue-specific immunity can be leveraged for developing targeted therapeutics.

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Section: Methods and Computational Approaches In Systems Immunologymentioning

confidence: 99%

The Whole Body as the System in Systems Immunology

Poon

Farber

2020

iScience

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“…Comparing B cell profiles by flow cytometry analysis revealed differential expression of key B cell markers delineating specific B cells subsets in the airways and blood ( Figure S5A, S5B). In particular, airway B cells exhibited increased expression of CD69, a marker expressed by human tissue resident B cells (Weisel et al, 2020), and activation markers CD86 and CD95 ( Figure S5A, S5B). Phenograph clustering further delineated subsets of activated and tissue-resident B cells present in airways, while blood contained higher frequencies of CXCR5 + and naïve B cells ( Figure S5C-E).…”

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confidence: 99%

Analysis of respiratory and systemic immune responses in COVID-19 reveals mechanisms of disease pathogenesis

Szabo

Dogra

Gray

et al. 2020

Preprint

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Immune responses to respiratory viruses like SARS-CoV-2 originate and function in the lung, yet assessments of human immunity are often limited to blood. Here, we conducted longitudinal, high-dimensional profiling of paired airway and blood samples from patients with severe COVID-19, revealing immune processes in the respiratory tract linked to disease pathogenesis. Survival from severe disease was associated with increased CD4+T cells and decreased monocyte/macrophage frequencies in the airway, but not in blood. Airway T cells and macrophages exhibited tissue-resident phenotypes and activation signatures, including high level expression and secretion of monocyte chemoattractants CCL2 and CCL3 by airway macrophages. By contrast, monocytes in blood expressed the CCL2-receptor CCR2 and aberrant CD163+ and immature phenotypes. Extensive accumulation of CD163+monocyte/macrophages within alveolar spaces in COVID-19 lung autopsies suggested recruitment from circulation. Our findings provide evidence that COVID-19 pathogenesis is driven by respiratory immunity, and rationale for site-specific treatment and prevention strategies.

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“…To explore this idea, we conducted an extensive phenotypic analysis using mass cytometry on circulating peripheral blood (Figure 4). The CD45RB isoform detected by the Ab clone MEM-55 was reported as an accurate marker to identify not only CD27and CD27 + MBCs (43,44) but also MZB cell lineage subsets (45,46). We thus used a routine panel of 35 markers including anti-CD45RB (MEM-55) Ab and the intracellular detection of T-BET on whole blood from seven different donors (Figure 4A).…”

Section: Cd45rb Cd1c and Unique Homing Receptor Profile Identify A Circulating Cd27marginal Zone B-cell-related Progenitor Populationmentioning

confidence: 99%

IL-21 and IFN-alpha have both opposite and redundant role on human innate precursors and memory B-cell differentiation

Boudigou¹,

Michée-Cospolite²,

Hémon³

et al. 2021

Preprint

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Immunological memory is essential for effective immune protection upon antigen rechallenge. Memory B cells encompass multiple subsets, heterogeneous in terms of phenotypes, origins and precursors, anatomical localization, and functional responses. B-cell responses are conditioned by micro-environmental signals, including cytokines. Here, we analyzed in vitro the effects of two cytokines implicated in B-cell differentiation, interferon-alpha (IFN-α) and interleukin (IL)-21, on the early functional response of four different mature B-cell subsets (IgD- CD27- naive, IgD+ CD27+ unswitched, IgD- CD27+ switched and double-negative B cells). The dual response of naive and memory B cells to IL-21 allowed us to uncover a unique IgD+ CD27- CD10- B-cell population (referred to as NARB+) characterized by the expression of marginal zone B-cell markers CD45RB and CD1c. Similar to memory B cells, NARB+ cells were in a pre-activated state, allowing them to rapidly differentiate into plasmablasts upon innate signals while maintaining their susceptibility to IL-21 activation-induced apoptosis as observed for the naive compartment. Both in-depth phenotypic analysis of circulating B cells, and identification of these cells in spleen, tonsil and gut-associated lymphoid tissues, supported that NARB+ are uncommitted precursors of human marginal zone B cells.

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Comprehensive analyses of B-cell compartments across the human body reveal novel subsets and a gut-resident memory phenotype

Cited by 88 publications

References 46 publications

The Whole Body as the System in Systems Immunology

The Whole Body as the System in Systems Immunology

Analysis of respiratory and systemic immune responses in COVID-19 reveals mechanisms of disease pathogenesis

IL-21 and IFN-alpha have both opposite and redundant role on human innate precursors and memory B-cell differentiation

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