The Cell-Intrinsic Circadian Clock Is Dispensable for Lymphocyte Differentiation and Function

Cell Rep. 2015 Jun 9;11(9):1339-49. doi: 10.1016/j.celrep.2015.04.058. Epub 2015 May 21.


Circadian rhythms regulate many aspects of physiology, ranging from sleep-wake cycles and metabolic parameters to susceptibility to infection. The molecular clock, with transcription factor BMAL1 at its core, controls both central and cell-intrinsic circadian rhythms. Using a circadian reporter, we observed dynamic regulation of clock activity in lymphocytes. However, its disruption upon conditional Bmal1 ablation did not alter T- or B-cell differentiation or function. Although the magnitude of interleukin 2 (IL-2) production was affected by the time of bacterial infection, it was independent of cell-intrinsic expression of BMAL1. The circadian gating of the IL-2 response was preserved in Bmal1-deficient T cells, despite a slight reduction in cytokine production in a competitive setting. Our results suggest that, contrary to the prevailing view, the adaptive immune response is not affected by the cell-intrinsic clock but is likely influenced by cell-extrinsic circadian cues operating across multiple cell types.

Publication types

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

MeSH terms

  • ARNTL Transcription Factors / deficiency
  • Animals
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology*
  • Cell Differentiation / immunology*
  • Circadian Clocks / immunology*
  • Flow Cytometry
  • Mice
  • Mice, Knockout
  • Polymerase Chain Reaction
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*


  • ARNTL Transcription Factors