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Mus musculus

ABSTRACT: T cell help controls the speed of the cell cycle in germinal center B cells.

PROVIDER: PRJNA290858 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR2125810_1.fastq.gz	Fastqsanger.gz
	SRR2125810_2.fastq.gz	Fastqsanger.gz
	SRR2125811_1.fastq.gz	Fastqsanger.gz
	SRR2125811_2.fastq.gz	Fastqsanger.gz
	SRR2125804_1.fastq.gz	Fastqsanger.gz

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T cell help controls the speed of the cell cycle in germinal center B cells.

Project description:The germinal center (GC) is a microanatomical compartment wherein high-affinity antibody-producing B cells are selectively expanded. B cells proliferate and mutate their antibody genes in the dark zone (DZ) of the GC and are then selected by T cells in the light zone (LZ) on the basis of affinity. Here, we show that T cell help regulates the speed of cell cycle phase transitions and DNA replication of GC B cells. Genome sequencing and single-molecule analyses revealed that T cell help shortens S phase by regulating replication fork progression while preserving the relative order of replication origin activation. Thus, high-affinity GC B cells are selected by a mechanism that involves prolonged dwell time in the DZ where selected cells undergo accelerated cell cycles. To determine whether GC B cells receiving high levels of T cell help show a specific change in gene expression, we compared DZ cells in the G1 phase of the cell cycle from αDEC-OVA and control αDEC-CS treated GCs using a fluorescent ubiquitination-based cell cycle indicator (Fucci-tg). RNA sequencing revealed that T cell-mediated selection produced an increase in gene expression programs associated with the cell cycle, metabolism, including the metabolism of nucleotides, and genes downstream of c-Myc and the E2F transcription factors.

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