SubsidieMeestersEarly life imprinting of B cell memory and its role in adult immunity
This project aims to investigate how early life derived B cells (ELO-B) shape adult immune responses through their unique imprinting and contributions to immunological memory and tolerance.
Projectdetails
Introduction
This proposal addresses the combined role of early life derived B cells in the adult immune system. Neonatal immune imprinting is now a 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.
B Cells and Immunological Memory
Despite the ability of B cells to integrate and store complex immunological memory for a lifetime, surprisingly little is known about their 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.
Findings and Implications
These findings reveal pervasive neonatal antigenic imprinting of the adult B cell compartment, challenging the assumption that the adaptive immune system is naïve 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 adult immunity.
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.
Aims of the Research
- 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.
Financiële details & Tijdlijn
Financiële details
| Subsidiebedrag | € 1.999.983 |
| Totale projectbegroting | € 1.999.983 |
Tijdlijn
| Startdatum | 1-6-2024 |
| Einddatum | 31-5-2029 |
| Subsidiejaar | 2024 |
Partners & Locaties
Projectpartners
- LUNDS UNIVERSITETpenvoerder
Land(en)
Vergelijkbare projecten binnen European Research Council
| Project | Regeling | Bedrag | Jaar | Actie |
|---|---|---|---|---|
Deciphering the antibody-microbiota axis in early lifeThis project aims to explore how early life immune exposures shape immunoglobulin repertoires and their impact on health, particularly allergies, by analyzing B cell receptor sequences and microbiota antigens. | ERC Starting... | € 1.650.000 | 2023 | Details |
Immune mechanisms of experience induced brain plasticity: the contribution of brain resident T cellsThis project aims to explore how environmental enrichment influences brain T cells and their role in neuroplasticity, ultimately developing immunotherapy strategies for neurodevelopmental disorders. | ERC Starting... | € 1.499.650 | 2025 | Details |
Engineered symbionts elucidate gut T cell memory and its (dys)regulationThe GuT Memory project aims to uncover the mechanisms of microbiota-directed Th cell memory to enhance vaccine design and target pathogenic T cells in inflammatory bowel disease. | ERC Starting... | € 1.600.683 | 2024 | Details |
Innate lymphoid cells and tissue adaptation to changing metabolic needsThis project aims to elucidate the role of ILC3 and the IL-22:IL-22BP module in intestinal adaptation to metabolic changes, with implications for understanding and treating metabolic diseases. | ERC Advanced... | € 2.379.266 | 2022 | Details |
Activation and switch of fates in T lymphocytes.This project aims to model the fate choices of naïve and memory CD8+ T cells using experimental immunology and systems biology to enhance vaccine design and improve responses to infections and cancer. | ERC Consolid... | € 2.625.000 | 2025 | Details |
Deciphering the antibody-microbiota axis in early life
This project aims to explore how early life immune exposures shape immunoglobulin repertoires and their impact on health, particularly allergies, by analyzing B cell receptor sequences and microbiota antigens.
Immune mechanisms of experience induced brain plasticity: the contribution of brain resident T cells
This project aims to explore how environmental enrichment influences brain T cells and their role in neuroplasticity, ultimately developing immunotherapy strategies for neurodevelopmental disorders.
Engineered symbionts elucidate gut T cell memory and its (dys)regulation
The GuT Memory project aims to uncover the mechanisms of microbiota-directed Th cell memory to enhance vaccine design and target pathogenic T cells in inflammatory bowel disease.
Innate lymphoid cells and tissue adaptation to changing metabolic needs
This project aims to elucidate the role of ILC3 and the IL-22:IL-22BP module in intestinal adaptation to metabolic changes, with implications for understanding and treating metabolic diseases.
Activation and switch of fates in T lymphocytes.
This project aims to model the fate choices of naïve and memory CD8+ T cells using experimental immunology and systems biology to enhance vaccine design and improve responses to infections and cancer.