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Early life imprinting of B cell memory and its role in adult immunity

Objective

This proposal addresses the combined role of early life derived B cells in the adult immune system. Neonatal immune imprinting is now well-established concept. It emphasizes the importance of the early life window to establish host-microbial mutualism and the set-point for immune responsiveness later in life. However, the cellular and molecular mechanisms underlying this immune programming are not well understood. Despite the ability of B cells to integrate and store complex immunological memory for a lifetime, surprisingly little is known about its ability to confer the longitudinal effects of neonatal microbial instruction.

By time-stamping B cells that arise early in life, my research team resolved a self-sustaining network of IgM and IgA B and plasma cells that carry memory of neonatal exposure. Such early life origin B (ELO-B) cells are unevenly distributed among immunophenotypically and anatomically defined B cell subsets and make up a substantial portion of the adult B cell pool in unimmunized mice. These findings reveal pervasive neonatal antigenic imprinting of the adult B cell compartment, challenging the assumption that the adaptive immune system is nave in the absence of deliberate immunization. With this understanding arises an urgent need to dissect the formation and function of ELO-B cell memory and their lasting impact on host protection and long-term homeostasis. To this end, we have built an unprecedented genetic toolkit leveraging the power of our time-stamping approach, to track and manipulate ELO-B cell responses without perturbing adul
Overarching hypothesis: ELO-B cells uniquely imprinted by developmental and microbial determinants early in life shape the trajectory of adult immune responses in health and disease.

Aim 1. Dissecting the formation of a complex ELO-B cell layer.

Aim 2. Tracing ELO-B cell derived antibodies and their contribution to adult B cell responses.

Aim 3. Defining the role for ELO-B cells in immunological tolerance.

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HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

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(opens in new window) ERC-2023-COG

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Host institution

LUNDS UNIVERSITET
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.

€ 1 999 983,00
Address
Paradisgatan 5c
22100 Lund
Sweden

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Region
Södra Sverige Sydsverige Skåne län
Activity type
Higher or Secondary Education Establishments
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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.

€ 1 999 983,00

Beneficiaries (1)

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