In vitro generation of long-lived human Plasma Cells II
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PROVIDER: PRJNA923678 | ENA |
REPOSITORIES: ENA
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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: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
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2012-10-18 | GSE41208 | GEO
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Project description:Maturation of Long Lived Plasma cells
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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: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.
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Project description:Upon encounter with antigen, B cells undergo a sequential process of differentiation to become antibody-secreting plasma cells. While the key drivers of differentiation have been identified, research has been limited by the lack of in vitro models recapitulating the full process for murine B cells. Here we describe methodology using BCR or TLR ligation to obtain plasma cells that are phenotypically mature, have exited cell cycle and express a gene signature concordant with long-lived plasma cells. Dependent on the initial stimuli, the transcriptomes also show variation, suggestive of unique functional properties for the resultant plasma cells. Moreover, using the new culture conditions we demonstrate that alternative promoter choice regulating the expression of the master transcription factor Blimp-1 can be observed. Thus, our novel system provides a readily tractable model for furthering our understanding of plasma cell biology.
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Project description:We report that there are differences in V gene usage in memory B cells and long-lived plasma cells after oral immunization. The hapten NP was conjugated to cholera toxin (CT) to create NP-CT, an antigen that is highly immunogenic after oral immunization. The NP hapten induces immune responses dominated by the 1-72 (VH186.2) heavy chain V region. The relationship between NP binding IgA antibody genes from memory B cells from spleen, MLN and Peyer´s patches and long-lived plasma cells from lamina propria and bone marrow that persisted 6-12 months after an oral immunization in three C57BL/6 mice with NP-CT was investigated. Extensive clonal overlap im clones was observed between long-lived memory cells from lamina propria and bone marrow, but very limited overlap was found between memory cells and plasma cells. The data suggest that memory and plasma cells formed through temporarily or anatomically separate processes.
2016-08-18 | GSE84698 | GEO
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