Myeloid Skewing in Aging Bone Marrow Depends on Long-lived Plasma Cell Accumulation
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PROVIDER: PRJNA449533 | ENA |
REPOSITORIES: ENA
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Project description:Aging results in a reduction in B lymphopoiesis and an increase in myelopoiesis in mice and humans. We investigated how cellular changes in the aging hematopoietic microenvironment contribute to these alterations in hematopoiesis and found that long-lived plasma cells (LLPCs) increase in number in the bone marrow of old mice. The LLPCs exhibited a Toll Like Receptor activation signal, and their accumulation was partially dependent on inflammatory cytokines. LLPCs were able to stimulate myelopoiesis from hematopoietic stem cells and myeloid progenitors in vitro, and anti-CD138 antibody-mediated depletion of LLPCs or blockade of pro-inflammatory signaling in old mice in vivo resulted in a significant reduction in LLPC number and attenuated myeloid development. However, B lymphopoiesis remained suppressed. These data identify the increase in LLPC number as obligate for age-associated increases in myelopoiesis and provide evidence that, in the context of aging, enhanced myelopoiesis and depressed lymphopoiesis are distinct, independently regulated processes.
2019-07-16 | GSE112939 | GEO
Project description:Splenic long-lived plasma cells (PCs) are abnormally numerous and deleterious in systemic autoimmune diseases, yet how they accumulate remains poorly understood. We demonstrate here that a pathological role of spleen-derived CD11b+Gr-1+ myeloid cells (SPMCs) underpins the accumulation of splenic long-lived PCs in a lupus-prone model. SPMCs were a mixture of granulocytic and monocytic myeloid-derived suppressor cells (MDSCs) that were expanded and acquired proinflammatory phenotypes in situ during lupus progression. By promoting the development of IFN--secreting and follicular helper T cells, SPMCs licensed CD4+ T cells to be pathologic activators of SPMCs and PCs. SPMCs also directly promoted the survival of PCs by providing B-cell activating factor of the TNF family. The frequency of SPMCs correlated with that of splenic long-lived PCs. Depletion of CD11b+Gr-1+ cells reduced autoantibody production. Thus, our findings suggest that SPMCs expanded in situ establish a positive feedback loop with CD4+ T cells, leading to accumulation of long-lived PCs which exacerbate lupus autoimmunity.
2021-02-09 | GSE161850 | GEO
Project description:To analyze global gene transcriptional changes and BCR clonal differences associated with long lived plasma cell specification, we sorted LLPCs and bulk PCs using Blimp1-ERT2-cre rosa26-LSLYFP expressing mice and analyzed them using bulk RNAsequencing
2024-02-22 | GSE221251 | GEO
Project description:Previous data have suggested that B-cell–depletion therapy may induce the settlement of autoreactive long-lived plasma cells (LLPCs) in the spleen of patients with autoimmune cytopenia. To investigate this process, we used the AID-CreERT2-EYFP mouse model to follow PCs engaged in an immune response. Multiplex-PCR at the single-cell level revealed that only a small fraction of splenic PCs had a long-lived signature, whereas PCs present after anti-CD20 antibody treatment appeared more mature, similar to bone-marrow PCs. It suggested that, in addition to a process of selection, a maturation induced upon B-cell depletion drove PCs toward a long-lived program. We showed that BAFF and CD4+ T cells play a major role in PC survival niche, because combining anti-CD20 with anti-BAFF or anti-CD4 antibody greatly reduce the number of splenic PCs. Similar results were obtained in the lupus-prone NZB/W model. These different contributions of soluble and cellular components of the PC niche in the spleen demonstrate that the LLPC expression profile is not cell-intrinsic but largely depends on signals provided by the splenic microenvironment, implying that interfering with these components at the time of B cell depletion might improve the response rate in autoimmune cytopenia.
2018-02-19 | E-MTAB-6449 | biostudies-arrayexpress
Project description:Gene expression profiling of B-cells from a model differentiation series: from Naïve B-cells, through a proliferative plasmablast stage to long-lived antibody secreting plasma cells. B-cells were isolated from the peripheral blood of three adult donors and differentiated in vitro (see individual samples for culture conditions)
2012-10-18 | E-GEOD-41208 | biostudies-arrayexpress
Project description:Background: Skewing root patterns provide key insights into root growth strategies and mechanism that produce root architectures Roots exhibit skewing and waving when grown on a tilted, impenetrable surface, and while the genetics guiding these morphologies have been examined, the underlying molecular mechanisms of skewing and waving remain unclear. In this study, transcriptome data were derived from two Arabidopsis ecotypes, WS and Col-0, under three tilted growth conditions in order to identify candidate genes involved in skewing. WS is a skewing ecotype. Col-0 is a non-skewing ecotype. Results: This work identifies a number of genes that are likely involved in skewing, using growth conditions that differentially affect skewing and waving. Comparing the gene expression profiles of WS and Col-0 in different tilted growth conditions identified 11 candidate genes as potentially involved in the control of skewing. These 11 genes are involved in several different cellular processes, including sugar transport, salt signaling, cell wall organization, and hormone signaling. Conclusions: Many of the 11 identified genes are involved in signaling and perception, rather than the physical restructuring of roots, leading to the conclusion that root skewing is enabled through diverse environmental signaling pathways. These findings revealed further insights into the molecular mechanisms behind root skewing. This work investigated the transcriptional differences between skewing and non-skewing roots. Comparisons within WS revealed gees that that responded to the angle of growth (Agp) during the process of skewing. These genes were cross referenced with transcripts differing between the WS and Col-0 genotypes to refine the list of genes that are most probably be involved in root skewing. More of the highly probable skew gene candidates (HPSGC) are associated with environmental sensing (e.g. salt, sugar, hormones, darkness) than with physical growth differences (e.g. cell wall remodeling, cell division, cell elongation). Thus, the root behavior of skewing appears to be primarily driven by pathways that respond to disparate signals from the root local environment. Future studies could investigate the HPSGC to find the specific pathways and molecular mechanisms contributing to root skewing.
2016-08-31 | GSE83242 | GEO
Project description:Gene expression profiling of B-cells from a model differentiation series: from Naïve B-cells, through a proliferative plasmablast stage to long-lived antibody secreting plasma cells.
2012-10-18 | GSE41208 | GEO
Project description:Gene expression profiling of B-cells from a model differentiation series: from Naïve B-cells, through a proliferative plasmablast stage to long-lived antibody secreting plasma cells.
2023-12-31 | GSE222862 | GEO
Project description:Summary: Long-lived IgE plasma cells reside in the bone marrow of allergic mice and atopic humans, confer IgE serological memory and produce allergen-specific IgE that can drive anaphylaxis. Abstract: Immunoglobulin E (IgE) plays an important role in allergic diseases. Nevertheless, the source of IgE serological memory remains controversial. We re-examined the mechanism of serological memory in allergy using a dual-reporter system to track IgE plasma cells (PCs) in mice. Short-term allergen exposure resulted in the generation of IgE plasma cells that resided mainly in secondarylymphoid organs and produced IgE that was unable to degranulate mast cells. In contrast, chronic allergen exposure led to the generation of long-lived IgE plasma cells that were primarily derived from sequential class switching of IgG1, accumulated in the bone marrow (BM) and produced IgE capable of inducing anaphylaxis. Most importantly, IgE plasma cells were found in the BM of human allergic, but not non-allergic donors, and allergen-specific IgE produced by these cells was able to induce mast cell degranulation when transferred to mice. These data demonstrate that longlived IgE BMPCs arise during chronic allergen exposure and establish serological memory in both mice and humans.
2019-11-16 | GSE140435 | GEO
Project description:Chronic allergen exposure drives accumulation of long-lived IgE plasma cells in the bone marrow, giving rise to serological memory
| PRJNA589740 | ENA