Endogenous Nur77 Is a Specific Indicator of Antigen Receptor Signaling in Human T and B Cells

J Immunol. 2017 Jan 15;198(2):657-668. doi: 10.4049/jimmunol.1601301. Epub 2016 Dec 9.


Distinguishing true Ag-stimulated lymphocytes from bystanders activated by the inflammatory milieu has been difficult. Nur77 is an immediate early gene whose expression is rapidly upregulated by TCR signaling in murine T cells and human thymocytes. Nur77-GFP transgenes serve as specific TCR and BCR signaling reporters in murine transgenic models. In this study, we demonstrate that endogenous Nur77 protein expression can serve as a reporter of TCR and BCR specific signaling in human PBMCs. Nur77 protein amounts were assessed by immunofluorescence and flow cytometry in T and B cells isolated from human PBMCs obtained from healthy donors that had been stimulated by their respective Ag receptors. We demonstrate that endogenous Nur77 is a more specific reporter of Ag-specific signaling events than the commonly used CD69 activation marker in both human T and B cells. This is reflective of the disparity in signaling pathways that regulate the expression of Nur77 and CD69. Assessing endogenous Nur77 protein expression has great potential to identify Ag-activated lymphocytes in human disease.

Publication types

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

MeSH terms

  • Animals
  • B-Lymphocytes / immunology*
  • Blotting, Western
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Humans
  • Lymphocyte Activation / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Nuclear Receptor Subfamily 4, Group A, Member 1 / immunology*
  • Receptors, Antigen / immunology
  • T-Lymphocytes / immunology*


  • NR4A1 protein, human
  • Nuclear Receptor Subfamily 4, Group A, Member 1
  • Receptors, Antigen