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

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 adulOverarching 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.