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Memory and innate-like B-cell subsets: deciphering a multi-layered B-cell response in mice and humans

Project description

Understanding B-cell responses

Vaccination has greatly improved human health by inducing antibody production from memory B-cells and long-lived plasma cells. However, little is known about the diversity and longevity of memory B-cell subsets and the factors that influence them. Funded by the European Research Council, the B-cell response project aims to address these questions by studying different B-cell subsets and helper T-cells in various conditions. Researchers will investigate the lifelong persistence of B-cell memory to identify specific transcriptional programmes and identify unique pathways linked to immune responses. The work will unveil the regulatory pathways of B-cell subsets, offering important insight into their pathological or beneficial mobilisation.

Objective

B cells are the main actors of successful vaccines, and their protective capacity relies on several subsets with innate-like and memory properties that fulfill different effector functions. In the present project, we wish to develop approaches in both mice and humans, to confront the similarities and the differences of their B cell responses.

The three aims proposed are:
1) To study the different B cell subsets and TFH cells engaged in a memory response through the use of a new mouse reporter line allowing their irreversible labeling (inducible Cre recombinase under the control of the Bcl6 gene): this will be performed in different conditions of TH1 vs. TH2 polarization, as well as during a chronic viral infection, in which virus-specific antibodies have been shown to be required to control the disease (in collaboration with D. Pinschewer, Basel)
2) To study whether the lifelong persistence of B cell memory, as occurs for memory B cells against smallpox that we can obtain at high purity from aged donor's spleens, corresponds to a specific transcriptional program at the miRNA, lncRNA or mRNA level, as well as a specific cell homeostasis
3) To discriminate the specific effector function of human marginal zone and IgM memory B cells in, respectively, T-independent and T-dependent responses, as well as their specific differentiation/diversification pathway.

The general goal is to delineate the regulatory pathways leading to the activation and persistence of the different B cell subsets, allowing for a better understanding of the conditions leading to their pathological or beneficial mobilization.

Fields of science (EuroSciVoc)

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Programme(s)

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Topic(s)

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Funding Scheme

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ERC-ADG - Advanced Grant

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Call for proposal

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(opens in new window) ERC-2015-AdG

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Host institution

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 2 098 750,00
Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 2 098 750,00

Beneficiaries (1)

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