By time-stamping B cells that arise early in life, we have successfully resolved a self-sustaining network of early life B cell memory. These 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 accounting for nearly half of all IgM and IgA plasma cells. Our findings reveal pervasive neonatal antigenic imprinting of the adult B cell compartment challenging the assumption that adaptive immune system is naïve in the absence of deliberate immunization. These findings provide a new conceptual framework for deconvoluting B cell responses in health and disease. Their publication the journal Immunity in 2022 and marks the successful delivery of the number one objective of FateMapB.
In addition we have demonstrated that the developmentally restricted expression of Lin28b temporarily relaxes the autoimmune checkpoint during B cell development allowing for augmented B cell positive selection and peripheral output (Science Immunology 2019). Thus, Lin28b breeches the censorship of developing B cells with perceived self-antigen engagement and the output of poly-reactive B-1 cells early in life. Furthermore, ectopic Lin28b expression in adult B cell precursors reinitiates the fetal-like augmented state of positive selection. The latter was quantified using cellular barcoding, a single cell lineage tracing method allowing for the relative quantification of precursor-progeny ratio of pre- and post-selection B cells in vivo. We propose that this neonatal mode of B cell selection represents a cell intrinsic cue to accelerate the de novo establishment of the adaptive immune system and incorporate a layer of natural antibody mediated immunity throughout life.
