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In vitro generation of long-lived human Plasma Cells II

ABSTRACT: In vitro generation of long-lived human Plasma Cells II

PROVIDER: PRJNA923678 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR23076300.fastq.gz	Fastqsanger.gz
	SRR23076301.fastq.gz	Fastqsanger.gz
	SRR23076302.fastq.gz	Fastqsanger.gz
	SRR23076303.fastq.gz	Fastqsanger.gz
	SRR23076304.fastq.gz	Fastqsanger.gz

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In vitro generation of long-lived human Plasma Cells

Project description:Gene expression profiling of B-cells from a model differentiation series: from NaÃ¯ve 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

In vitro generation of long-lived human Plasma Cells II

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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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The B cell maturation antigen (BCMA) is dispensable for long-lived plasma cell survival

Project description:Survival of antibody-secreting plasma cells is a prerequisite to establish long-lasting humoral immune protection. The B cell maturation antigen (BCMA) has been proposed to promote APRIL-mediated survival signals in plasma cells. However, the extensive shedding of murine BCMA from the plasma cell surface raises doubts about its ability to function as a signaling receptor. To unequivocally establish whether BCMA is required for long-lived plasma cell survival, we established two independent BCMA-deficient mouse lines and analyzed the survival of antigen-specific plasma cells after immunization. In contrast to published data, we found comparable numbers of long-lived antigen-specific plasma cells after primary and secondary protein and mRNA immunizations in BCMA-deficient mice. In addition, wildtype and BCMA-deficient plasma cells showed comparable transcriptome profiles with no indication for reduced survival signaling. Interestingly, total plasma cell numbers were increased after boost immunization in bone marrow and mesenteric lymph nodes of BCMA-deficient mice. Therefore, BCMA has no intrinsic role in maintaining long-lived plasma cells. We propose a function of BCMA limited to acting as a soluble decoy receptor for APRIL and fine-tuneing the size of the plasma cell population by limiting the availability of survival factors. This finding removes a piece of the puzzle of the mechanisms that contribute to long-lived plasma cell survival.

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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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