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Lineage tracking reveals origins and relative affinities of antibodies produced by two subsets of memory B cells

ABSTRACT: Lineage tracking reveals origins and relative affinities of antibodies produced by two subsets of memory B cells

PROVIDER: PRJNA729737 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR14522518.fastq.gz	Fastqsanger.gz
	SRR14522519.fastq.gz	Fastqsanger.gz
	SRR14522520.fastq.gz	Fastqsanger.gz
	SRR14522521.fastq.gz	Fastqsanger.gz
	SRR14522522.fastq.gz	Fastqsanger.gz

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Lineage tracking reveals origins and relative affinities of antibodies produced by two subsets of memory B cells

Project description:Memory B cells comprise a heterogenous group of cells that differ in origin, and phenotype. During the early phases of the immune response, activated B cells can differentiate into IgM expressing memory cells, short-lived plasma cells or seed germinal centers (GCs). The memory compartment is subsequently enriched by B cells that have been through several rounds of division and selection in the GC. Here we report on the use of an unbiased lineage tracking approach to explore the origins and properties of memory B cell subsets in mice with an intact immune system. We find that activated B cells continue to differentiate into memory B cells throughout the immune response. When defined on the basis of their origins, the memory B cells originating from activated B cells or GCs differ in isotype and overall gene expression, somatic hypermutation, and in their affinity for antigen.

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Therapeutic antibodies to ganglioside GD2 evolved from highly selective germline antibodies III

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BANCseq for determination of genome-wide apparent transcription factor binding affinities

Project description:This SuperSeries is composed of the SubSeries listed below. In vivo transcription factor binding is regulated by DNA sequence and chromatin features. However, the impact of chromatin context on genome-wide transcription factor binding affinities have not yet been characterized. Here we report the establishment of a quantitative protein-DNA binding assay to determine genome-wide binding affinities to native chromatinized DNA. We use this method to quantify apparent genome-wide binding affinities of both pioneering and non-pioneering transcription factors to uncover the regulatory role of chromatin on transcription factor binding. This revealed that DNA accessibility is the main determinant of transcription factor binding, which restricts nanomolar binding of non-pioneering factors to promoters. DNA binding motifs only appear to be important for very high-affinity binding, but are not essential for nanomolar binding. We uncover numerous biological processes enriched at specific binding affinities, suggesting they are regulated at defined transcription factor concentrations. Importantly, our method adds a new quantitative layer of transcription factor biology, enabling stratification of genomic targets based on transcription factor expression and prediction of transcription factor binding sites under non-physiological conditions, such as disease associated elevated expression of (onco)genes.

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