Exploring the role of Lin28b in the neonatal immune imprinting of B cells

The hygiene hypothesis proposes that abundant exposure to microbial antigens during early postnatal life is a prerequisite for the establishment of a tolerant immune system resilient to allergic and autoimmune diseases.

In this project we investigate the role of the developmentally restricted expression of the Lin28b gene in neonatal immune imprinting and its impact on long-term immune health.We have previously demonstrated the ability of Lin28b to re-shape the tolerance threshold of the primary B cell repertoire.

More recently, we discovered a critical role for Lin28b in the generation of immunoregulatory IL-10 producing B cells which function as potent gatekeepers against autoimmunity.

These unique insights have led us to hypothesize that early life origin (ELO) B cells potentiated by Lin28b are critical mediators of neonatal immune imprinting.

To test this, we employ an unparalleled mouse genetics toolkit to perturb Lin28b expression on the one hand, and track and manipulate the fates of ELO B cells on the other.

This in combination with experimental approaches for sterilizing immunity, anti-tumor immunity and autoimmunity makes it possible to establish causal links between the Lin28b / ELO B cell axis to long-term immune consequences.

The successful completion of this project is projected within a 5-year time frame and will generate molecular insights into neonatal immune imprinting and examine therapeutic prospects for ELO B cell targeting.