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

Immunity. 2020 Jul 14;53(1):217-232.e5. 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.

Keywords: B cells; cell atlas; human; mass cytometry; multi-omic; single cell.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • 5'-Nucleotidase / metabolism
  • Apyrase / metabolism
  • B-Lymphocyte Subsets / classification*
  • B-Lymphocyte Subsets / immunology*
  • CD11c Antigen / metabolism
  • Female
  • GPI-Linked Proteins / metabolism
  • Humans
  • Immunoglobulin Isotypes / metabolism*
  • Immunologic Memory / immunology
  • Leukocyte Common Antigens / metabolism
  • Membrane Proteins / metabolism*
  • Middle Aged
  • Signal Transduction / immunology
  • fas Receptor / metabolism


  • CD11c Antigen
  • FAS protein, human
  • GPI-Linked Proteins
  • Immunoglobulin Isotypes
  • Membrane Proteins
  • fas Receptor
  • Leukocyte Common Antigens
  • 5'-Nucleotidase
  • NT5E protein, human
  • Apyrase
  • ENTPD1 protein, human