Post-doctoral position for studying Human Long-term B-cell Memory - Institute Necker Enfants Malades (INEM)

Memory B cells generated by vaccines against viruses like smallpox (vaccinia virus) or yellow fever can persist for a lifetime in humans. It is so far unknown what specific gene expression program or metabolic status sustains such longevity. We have addressed this issue by the isolation of vaccinia virus specific B cells from the spleen of individuals vaccinated around 40 to 60 years before. This model is unique since it allows the study of memory B cells generated several decades ago that have never been restimulated with their cognate antigen.

RNA-seq of such samples has been already performed. The project will involve single cell analysis by multiplex RT-PCR to establish a transcriptional signature, metabolic studies based on mitochondrial and mitophagic activity of vaccinia virus-specific B cells compared to the bulk of IgG memory B cells, as well as analysis of telomere maintenance. Vaccinia virus-specific memory B cells elicited from recent immunizations will be analyzed in parallel to determine at what time a long-lived profile is acquired.

This subject has direct immunological implication but also general biological relevance since it consists in studying what is the nature of “normal immortal cells” which are neither senescent nor cancerous and can respond rapidly to a new antigenic challenge.

A strong expertise in molecular biology, flow cytometry, imaging as well as good skills in bioinformatics are required.

This project is developed within the team "Development of the immune system" headed by Claude-Agnès Reynaud and Jean-Claude Weill, Institut Necker-Enfants Malades (Paris), and is funded by an ERC Advanced Grant that will support the post-doctoral position.

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