Establishment of early life humoral immunity in homeostasis and in the context of enteric virus infection

The neonatal immune system is uniquely suited to the enormous challenge of de novo antigen encounter by balancing host protection and tolerance establishment. However, some infectious agents such as rotavirus can effectively overcome the protection of young infants. IgA-driven humoral immunity in babies at steady state derives almost exclusively from mother´s milk.

Yet, neonatal natural rotavirus infections and vaccinations lead to powerful humoral immune memory.

The "hygiene hypothesis" gave birth to the idea that early life induced immunity has strong effects on life-long immune health.

Today, we know that healthy induction protecting from autoimmunity and allergy later in life requires a “weaning reaction” during a specific “window of opportunity”.

Despite the rising urgency and popular interest in the topic, the cellular and molecular basis for neonatal humoral immune imprinting is not understood.

We aim to focus on the temporal requirements for humoral immune induction on the intestinal wall during the first stage of life in the context of homeostasis and infection.

Our preliminary findings that early life IgA induced by rotavirus infection or by the lack of antibodies in mother´s milk strongly depends on T cell help suggest a level of complexity higher than previously anticipated with putative effects lasting into adulthood.

Complicated breeding and time mating as well as in-depth mechanistic analysis in vivo require the long term financial investment applied for here.