Spatial Map of Human B Cell and Plasma Cell Compartments

Abstract Naive B cells differentiate into antibody secreting plasma cells (PC) and memory B cells (MBC) that together dictate the quality and persistence of the humoral immune response. However, a comprehensive analysis of human B lineage population structure that integrates surface phenotype and intracellular functional status is lacking. One reason for this knowledge gap is the difficulty of obtaining diverse tissues from normal individuals. Here we have performed a comprehensive analysis of human lymphoid tissue from relatively inaccessible sites including SPL, BM and LN to visualize B cell organization across diverse tissues from normal donors. We exploited a novel algorithmic pipeline for unbiased analysis. Further, we are aligning findings across mouse and man. Here we report the identification of select markers that are involved in a shared BM precursor/PC program including CD28, CLEC12A, CCR2, CD7 and CD79b by LEGENDScreening. We have validated these markers by RNA-seq analysis of murine splenic PC and conventional flow cytometry analysis of human gut PC. We hypothesize that long-lived PCs returning to BM extinguish the B cell program and re-engage with the ancestral long-lived program. Overall, our findings constitute the basis for a geographic understanding of human B lineage population structure that will inform studies on the human humoral immune response and the mechanisms of PC longevity.