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Two subsets of human marginal zone B cells resolved by global analysis of lymphoid tissues and blood

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE193869 | GEO | 2022/01/21

REPOSITORIES: GEO

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Two subsets of human marginal zone B cells resolved by global analysis of lymphoid tissues and blood [healthy and lupus human blood]

Project description:B cells generate antibodies that are essential for immune protection, but their subgroups are poorly defined. Here we perform undirected deep profiling of B cells in matched human lymphoid tissues from deceased transplant organ donors and blood. In addition to identifying unanticipated features of tissue-based B cell differentiation, we resolve two subsets of marginal zone B (MZB) cells differing in cell surface and transcriptomic profiles, clonal relationships to other subsets, enrichment of genes in the NOTCH pathway, distribution bias within splenic marginal zone microenvironment, and immunoglobulin repertoire diversity and hypermutation frequency. Each subset is present in spleen, gut-associated lymphoid tissue, mesenteric lymph nodes, and blood. MZB cells and the lineage from which they are derived are depleted in lupus nephritis. Here we show that this depletion is of only one MZB subset. The other remains unchanged as a proportion of total B cells compared to health. Thus, it is important to factor MZB cell heterogeneity into studies of human B cell responses and pathology.

2022-01-21 | GSE193867 | GEO

Two subsets of human marginal zone B cells resolved by global analysis of lymphoid tissues and blood [human appendix, spleen, mLN]

2022-01-21 | GSE193868 | GEO

Two subsets of human marginal zone B cells resolved by global analysis of lymphoid tissues and blood

Project description:Two subsets of human marginal zone B cells resolved by global analysis of lymphoid tissues and blood

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Two subsets of human marginal zone B cells resolved by global analysis of lymphoid tissues and blood [healthy and lupus human blood]

Project description:Two subsets of human marginal zone B cells resolved by global analysis of lymphoid tissues and blood [healthy and lupus human blood]

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Two subsets of human marginal zone B cells resolved by global analysis of lymphoid tissues and blood [human appendix, spleen, mLN]

Project description:Two subsets of human marginal zone B cells resolved by global analysis of lymphoid tissues and blood [human appendix, spleen, mLN]

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Spatiotemporal segregation of human marginal zone and memory B cell populations in lymphoid tissue.

Project description:Human memory B cells and marginal zone (MZ) B cells share common features such as the expression of CD27 and somatic mutations in their IGHV and BCL6 genes, but the relationship between them is controversial. Here, we show phenotypic progression within lymphoid tissues as MZ B cells emerge from the mature naïve B cell pool via a precursor CD27-CD45RBMEM55+ population distant from memory cells. By imaging mass cytometry, we find that MZ B cells and memory B cells occupy different microanatomical niches in organised gut lymphoid tissues. Both populations disseminate widely between distant lymphoid tissues and blood, and both diversify their IGHV repertoire in gut germinal centres (GC), but nevertheless remain largely clonally separate. MZ B cells are therefore not developmentally contiguous with or analogous to classical memory B cells despite their shared ability to transit through GC, where somatic mutations are acquired.

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A temporally resolved transcriptome for developing "Keller" explants of the Xenopus laevis dorsal marginal zone.

Project description:BackgroundExplanted tissues from vertebrate embryos reliably develop in culture and have provided essential paradigms for understanding embryogenesis, from early embryological investigations of induction, to the extensive study of Xenopus animal caps, to the current studies of mammalian gastruloids. Cultured explants of the Xenopus dorsal marginal zone ("Keller" explants) serve as a central paradigm for studies of convergent extension cell movements, yet we know little about the global patterns of gene expression in these explants.ResultsIn an effort to more thoroughly develop this important model system, we provide here a time-resolved bulk transcriptome for developing Keller explants.ConclusionsThe dataset reported here provides a useful resource for those using Keller explants for studies of morphogenesis and provide genome-scale insights into the temporal patterns of gene expression in an important tissue when explanted and grown in culture.

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Marginal zone B cells regulate antigen capture by marginal zone macrophages.

Project description:The marginal zone (MZ) of the mouse spleen contains macrophages that express receptors that trap pathogens, including the scavenger receptor macrophage receptor with a collagenous structure and the C-type lectin specific intracellular adhesion molecule-grabbing nonintegrin receptor 1 (SIGN-R1). We previously reported that expression of SIGN-R1 was decreased in CD19-deficient mice. In this study, we demonstrate that SIGN-R1 is expressed on a subset of macrophage receptor with a collagenous structure (MARCO)(+) macrophages. This subset is diminished when MZ B cells are absent due to either genetic developmental defects or following transient migration of B cells out of the MZ. When B cells return to the MZ, there is a delay in recovery of SIGN-R1-expressing macrophages. During this period, capture of Ficoll, which for the macrophages requires SIGN-R1, remains defective not only by the macrophages, but also by the B cells. Thus, MZ B cells regulate expression of molecules on macrophages that are important for trapping Ag, which, in turn, is required for Ag capture by the B cells.

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Molecular characterization of Nodal marginal zone lymphoma

Project description:This SuperSeries is composed of the SubSeries listed below.

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Ly9 (CD229) Antibody Targeting Depletes Marginal Zone and Germinal Center B Cells in Lymphoid Tissues and Reduces Salivary Gland Inflammation in a Mouse Model of Sjogren's Syndrome.

Project description:Sjögren's Syndrome (SjS) is a common chronic autoimmune disease characterized by the B cell hyperactivation, lymphocyte infiltration, and tissue damage of exocrine glands. It can also present life-threatening extraglandular manifestations, such as pulmonary and hepatic involvement, renal inflammation and marginal zone (MZ) B cell lymphoma. Several biologic agents have been tested in SjS but none has shown significant efficacy. Here, we report the effects of Ly9 (CD229) antibody targeting, a cell surface molecule that belongs to the SLAM family of immunomodulatory receptors, using NOD.H-2h4 mice as a model of SjS-like disease. Female mice were treated with anti-Ly9 antibody or isotype control at week 24, when all mice present SjS related autoantibodies, salivary gland infiltrates, and marginal zone (MZ) B cell pool enlargement. Antibody injection depleted key lymphocyte subsets involved in SjS pathology such as MZ, B1, and germinal center B cells in spleen and draining lymph nodes without inducing a general immunosuppression. Importantly, mice receiving anti-Ly9 mAb showed a reduced lymphocyte infiltrate within salivary glands. This reduction may be, in part, explained by the down-regulation of L-selectin and alfa4/beta7 integrin induced by the anti-Ly9 antibody. Furthermore, levels of anti-nuclear autoantibodies were reduced after anti-Ly9 treatment. These data indicate that Ly9 is a potential therapeutic target for the treatment of SjS.

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