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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]

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE193867 | 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 [human appendix, spleen, mLN]

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 | GSE193868 | GEO

Human marginal zone B cell development from early T2 progenitors [MZBTraj]

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2021-01-31 | GSE163602 | GEO

Human marginal zone B cell development from early T2 progenitors [Pooled]

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Marginal zone B cells control follicular helper T cell response to high cholesterol diet

Project description:Splenic innate-like marginal zone B (MZB) cells are strategically positioned at the interface between the circulating blood and lymphoid tissue, where they initiate rapid immune responses to blood-borne antigens. Here, we find that selective genetic deletion of MZB cells substantially increases the follicular helper T (Tfh) cell and germinal center (GC) response to high cholesterol diet (HCD), which leads to T cell-dependent acceleration of atherosclerosis. We show that MZB cells activate a homeostatic program in response to HCD, in which upregulation of the transcription factor Atf3 plays a determinant regulatory role. Shuttling of MZB cells to the follicle is dispensable for their regulatory properties on Tfh cells. Instead, HCD promotes increased interaction between MZB and (pre-)Tfh cells outside the follicle, and upregulates MZB cell expression of Cd274 in an Atf3-dependent manner. Interaction between MZB and Tfh cells leads to Cd274-mediated suppression of Tfh cell motility, limits Tfh cell accumulation in the follicle and suppresses the pro-atherogenic Tfh/GC response. Our findings reveal a previously unsuspected role for MZB cells in the control of Tfh/GC response to a cholesterol diet, and uncover a new mechanism through which MZB cells can couple their unique metabolic and innate immune properties and use them to maintain a tolerogenic state. The results may have broad (patho)physiological implications.

2016-12-01 | GSE71699 | GEO

Transcriptome profiling of H3K27me3 demethylase deficient B cells

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2022-02-01 | GSE185095 | GEO

Crosstalk between murine marginal zone B cells, macrophages and CD8alpha+ dendritic cells promotes Listeria monocytogenes infection

Project description:Type 1 CD8α+ conventional dendritic cells (cDC1s) harbor and transport Listeria monocytogenes (LM) within the spleen and thereby promote infection; cDC1s are also required for CD8+ T cell priming. To test the role of the second lineage of splenic cDC in regulating infection or adaptive immunity to LM we used Dock8-deficient mice, which have impaired 33D1+ type 2 cDC (cDC2) function. We found reduced CD8+ T cell activation in Dock8-deficient mice, but this was not due to impaired cDC2 function but rather resistance to LM infection. Bacterial resistance was due to loss of marginal zone B (MZB) cells. We showed that IL-10 production by MZB cells did not alter antigen handling pathways in dendritic cells (DCs), including ones relevant for cross-priming or Listeria survival. Instead, IL-10 increased intracellular LM in macrophages in the marginal zone, which transfer bacteria to cDC1s. Bacteria-harboring cDC1s then traffic into the splenic white pulp where protection from sterilizing phagocytes promotes LM expansion. This work uncovers a unique crosstalk between the innate immune cells in the marginal zone, facilitated by IL-10, that promotes both infection but also CD8+ T cell activation.

2019-06-20 | GSE124771 | 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

| PRJNA798248 | ENA

Programming of marginal zone B cell fate by basic krüppel-like factor (BKLF/KLF3)

Project description:Gene expression analysis of splenic follicular B cells and marginal zone B cells from B6 and CD19:KLF3 transgenic mice Comparing KLF3-transgenic and non-transgenic follicular B cells by RNA-microarray revealed that KLF3 regulates a subset of genes that was similarly up-/downregulated upon normal MZ B cell differentiation. Indeed, KLF3 expression overcame the lack of MZ B cells caused by different genetic alterations, such as CD19-deficiency or blockade of B-cell activating factor (BAFF)-receptor signaling, indicating that KLF3 may complement alternative NF-κB signaling. Thus, KLF3 is a driving force towards MZ B cell maturation. RNA of splenic follicular B cells and marginal zone B cells were obtained from 4 different mice per group (B6 and CD19:KLF3 mice). 16 samples = 8 individual mice x 2 B cell subsets.

2011-01-29 | E-GEOD-26948 | biostudies-arrayexpress

Access to follicular dendritic cells is a pivotal step in murine chronic lymphocytic leukemia B cell activation and proliferation

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2014-09-01 | E-GEOD-60925 | biostudies-arrayexpress

Single-cell RNA sequencing of lymph node stromal cells reveals niche-associated heterogeneity

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2018-05-10 | GSE112903 | GEO

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