An Integrated Multi-omic Single-Cell Atlas of Human B Cell Identity
David R. Glass, Albert G. Tsai, John Paul Oliveria, Felix J. Hartmann, Samuel C. Kimmey, Ariel A. Calderon, Luciene Borges, Marla C. Glass, Lisa E. Wagar, Mark M. Davis, Sean C. Bendall
Abstract
B cells are capable of a wide range of effector functions including antibody secretion, antigen presentation, cytokine production, and generation of immunological memory. A consistent strategy for classifying human B cells by using surface molecules is essential to harness this functional diversity for clinical translation. We developed a highly multiplexed screen to quantify the co-expression of 351 surface molecules on millions of human B cells. We identified differentially expressed molecules and aligned their variance with isotype usage, VDJ sequence, metabolic profile, biosynthesis activity, and signaling response. Based on these analyses, we propose a classification scheme to segregate B cells from four lymphoid tissues into twelve unique subsets, including a CD45RB+CD27− early memory population, a class-switched CD39+ tonsil-resident population, and a CD19hiCD11c+ memory population that potently responds to immune activation. This classification framework and underlying datasets provide a resource for further investigations of human B cell identity and function.