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High recallability of memory B cells requires ZFP318-dependent transcriptional regulation of mitochondrial function

ABSTRACT: High recallability of memory B cells requires ZFP318-dependent transcriptional regulation of mitochondrial function

PROVIDER: PRJNA1086812 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR28299109_1.fastq.gz	Fastqsanger.gz
	SRR28299109_2.fastq.gz	Fastqsanger.gz
	SRR28299110_1.fastq.gz	Fastqsanger.gz
	SRR28299110_2.fastq.gz	Fastqsanger.gz
	SRR28299111_1.fastq.gz	Fastqsanger.gz

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High recallability of memory B cells requires ZFP318-dependent transcriptional regulation of mitochondrial function

Project description:Expression of the transcriptional regulator ZFP318 is induced in germinal center (GC)-exiting memory B cell precursors and memory B cells (MBCs). Using a conditional ZFP318 fluorescence reporter that also enables ablation of ZFP318-expressing cells, we found that ZFP318-expressing MBCs were highly enriched with GC-derived cells. Although ZFP318-expressing MBCs constituted only a minority of the antigen-specific MBC compartment, their ablation severely impaired recall responses. Deletion of the Zfp318 gene did not alter the magnitude of primary responses but markedly reduced MBC participation in recall. CD40 ligation promoted Zfp318 expression whereas BCR signaling was inhibitory. Enforced ZFP318 expression enhanced recall performance of MBCs that otherwise responded poorly. ZFP318-deficient MBCs expressed less mitochondrial genes, had structurally compromised mitochondria and were susceptible to reactivation-induced cell death. The abundance of ZFP318-expressing MBCs, instead of the number of antigen-specific MBCs, correlated with the potency of prime-boost vaccination. Therefore, ZFP318 controls the MBC recallability and represents a key checkpoint of humoral immune memory.

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High recallability of memory B cells requires ZFP318-dependent transcriptional regulation of mitochondrial function

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Zfp318 controls the recallability of memory B cells

Project description:Memory B cells (MBCs) are important for efficacious antibody-based vaccines and develop via germinal center (GC)-dependent and -independent routes. We find all MBCs are not equally recallable by antigen. Zfp318, a transcription regulator of spermatogenesis and IgD expression, is not expressed in GC B cells but upregulated in MBCs. GC-derived MBCs are far more recallable than GC-independent MBCs in a Zfp318-dependent manner. Zfp318 expression is inhibited by BCR but promoted by CD40 signaling, while its levels are positively correlated with B-cell receptor affinities. Enforced Zfp318 expression markedly increases the recallability of GC-independent MBCs. Zfp318-deficient MBCs show reduced expression of mitochondrion-related genes, exhibit lower mitochondrial membrane potentials, contain more structurally compromised mitochondria, and are susceptible to activation-induced cell death. The abundance of Zfp318-expressing MBCs positively correlates with the quality of vaccine-induced antibody immunity. Therefore, Zfp318 defines the recallability of the MBC compartment and represents a key regulator of humoral immune memory.

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High recallability of memory B cells requires ZFP318-dependent transcriptional regulation of mitochondrial function

Project description:High recallability of memory B cells requires ZFP318-dependent transcriptional regulation of mitochondrial function

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High recallability of memory B cells requires ZFP318-dependent transcriptional regulation of mitochondrial function

Project description:High recallability of memory B cells requires ZFP318-dependent transcriptional regulation of mitochondrial function

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High recallability of memory B cells requires ZFP318-dependent transcriptional regulation of mitochondrial function

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Zfp318 controls the recallability of memory B cells

Project description:Zfp318 controls the recallability of memory B cells