An Integrated Multi-omic Single-Cell Atlas of Human B Cell Identity

• Published in: Immunity (Cambridge, Mass.) Mass.), 2020-07, Vol.53 (1), p.217-232.e5
• Main Authors: Glass, David R., Tsai, Albert G., Oliveria, John Paul, Hartmann, Felix J., Kimmey, Samuel C., Calderon, Ariel A., Borges, Luciene, Glass, Marla C., Wagar, Lisa E., Davis, Mark M., Bendall, Sean C.
• Format: Article
• Language: English
• Subjects: 5'-Nucleotidase - metabolism; Antibodies; Antigen presentation; Antigens; Apyrase - metabolism; B cells; B-Lymphocyte Subsets - classification; B-Lymphocyte Subsets - immunology; Biosynthesis; Bone marrow; CD11c Antigen - metabolism; CD27 antigen; CD45RB antigen; cell atlas; Classification; Cytokines; fas Receptor - metabolism; Female; GPI-Linked Proteins - metabolism; human; Humans; Immunoglobulin Isotypes - metabolism; Immunologic Memory - immunology; Immunological memory; Immunology; Leukocyte Common Antigens - metabolism; Lymphocytes B; Lymphoid tissue; mass cytometry; Membrane Proteins - metabolism; Memory cells; Middle Aged; multi-omic; Signal Transduction - immunology; single cell; Tonsil
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/j.immuni.2020.06.013

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. [Display omitted] •A mass cytometry screen reveals 98 surface molecules expressed by human B cells•High-dimensional analysis identifies twelve B cell subsets across four tissues•CD45RB, CD11c, CD39, CD73, and CD95 define subsets of antigen-experienced B cells•Isotype usage, signaling, and metabolism vary in accordance with cell surface phenotype To identify molecules that distinguish functionally distinct subsets of human B cells, Glass et al. screened the expression of 351 surface molecules by mass cytometry. By combining identified molecules with functional readouts, they propose a new classification scheme to segregate B cells from four lymphoid tissues into twelve unique subsets.