In vitro generation of long-lived human Plasma Cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE41208 | GEO | 2012/10/18
SECONDARY ACCESSION(S): PRJNA176155
REPOSITORIES: GEO
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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.
2023-12-31 | GSE222862 | 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. 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
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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.
2021-11-03 | GSE160823 | GEO
Project description:The mechanisms whereby enteric pathogens and microbes induce systemic antibody responses remain obscure. In contrast to accepted models, we show that commensal microbes have a dramatic impact on the bone marrow (BM) plasma cell pool. Unlike standard vendor mice, in mice reared in our colony the majority of long-lived BM plasma cells secreted IgA antibodies. Exposing vendor mice to a unique microflora or Helicobacter sp. led to the generation of IgA-secreting BM cells, while also inducing increases in serum IgA antibodies enriched for binding to several commensal bacterial taxa. Moreover, BM IgA-secreting plasma cells exhibited a common clonal ancestry with intestinal IgA+ plasma cells, and both populations possessed unique gene expression signatures compared to other long-lived BM plasma cells. We conclude that commensal microbes overtly influence the BM plasma cell pool, and suggest that select commensal microbes can facilitate the induction of systemic humoral immunity.
2018-07-01 | GSE87091 | 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.
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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
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Project description:The differentiation of B cells into antibody-secreting cells depends on cell division-coupled, epigenetic and other cellular processes that are incompletely understood. We have developed a CRISPR/Cas9-based screen that models an early stage of T cell-dependent plasma cell differentiation and measures B cell survival or proliferation versus the formation of CD138+ plasmablasts. Here, we refined and extended this screen to more than 500 candidate genes that are highly expressed in plasma cells. Among known genes whose deletion preferentially affected plasmablast formation were the transcriptional regulators Prdm1, Irf4 and Pou2af1, and the Ern1 gene encoding the ER stress sensor IRE1a. Moreover, we newly identified several genes involved in NF-kB or p38 signaling (Pim2, Nfkbia, Mapk14), vesicle trafficking (Arf4, Preb) and epigenetic regulators that form part of the NuRD complexes (Hdac1, Mta2, Mbd2). Defective plasmablast formation caused by Ern1 deletion could not be rescued by spliced XBP1 (XBP1s), a transcription factor dependent on and downstream of IRE1a, suggesting that in early plasma cell differentiation IRE1a acts independently of XBP1s. The deletion of ARF4, a small GTPase required for ER-to-Golgi transport, impaired plasmablast formation by blocking antibody secretion. Plasmablast formation after Hdac1 deletion was consistently reduced by about 50%, while deletion of the closely related Hdac2 gene had no effect. Hdac1 knock-out led to strongly perturbed protein expression of antagonistic transcription factors that specify plasma cell versus B cell identity (by decreasing IRF4 and BLIMP1 and increasing BACH2 and PAX5). Taken together, our results highlight specific and non-redundant roles for Ern1, Arf4 and Hdac1 in the early steps of plasma cell differentiation.
2022-12-22 | PXD038201 | Pride
Project description:CD8 effector T cells with a CD127hi KLRG1- phenotype are considered precursors to the long-lived memory pool, while KLRG1+ CD127low cells are viewed as short-lived effectors. Nevertheless, we and others have shown that a KLRG1+ CD127low population persists into the memory phase and that these T cells (termed long-lived effector cells or LLEC) display robust protective function during acute re-challenge with bacteria or viruses. Whether these T cells represent a true memory population or are instead a remnant effector cell population that failed to undergo initial contraction has remained unclear. Here, we show that LLEC from mice express a distinct phenotypic and transcriptional signature that shares characteristics of both early effectors and long-lived memory cells. Furthermore, we find that LLEC are exclusively derived from day 12 KLRG1+ effector cells. Our work challenges the concept that the KLRG1+ CD127low population is dominated by short-lived cells and shows that KLRG1 downregulation is not a prerequisite to become a long-lived protective memory T cell.
2020-08-26 | GSE152841 | GEO