IDO expression by human B lymphocytes in response to T lymphocyte stimuli and TLR engagement is biologically inactive

Mol Immunol. 2011 Oct;49(1-2):253-9. doi: 10.1016/j.molimm.2011.08.017. Epub 2011 Sep 19.


The immune system must be under tight control to avoid undesired responses. The enzyme indoleamine 2,3-dioxygenase (IDO) can exert necessary regulating effects by catabolizing tryptophan, leading to the suppression of immune responses in different settings, such as pregnancy and tumor growth. IDO's immuno-suppressive actions are mediated by tryptophan starvation and the accumulation of toxic tryptophan metabolites, resulting in T cell anergy, inhibition of clonal expansion or apoptosis. IDO activity in human macrophages and dendritic cells has been observed after interaction with T lymphocytes, and is triggered by interferon-gamma (IFN-γ) as well as CD40-ligand (CD40L). However, it is unclear whether IDO activity is present in B lymphocytes, which have been identified as having suppressive properties involved in anti-tumor immunity inhibition. In this study, we investigated whether IDO expression is induced in human B cells after exposure to T lymphocyte stimuli and TLR ligands. We report IDO1 and IDO2 mRNA up-regulation by exogenous stimulation with CD40L and IFN-γ. IDO is also upregulated by imiquimod, a TLR 7/8 agonist. In addition, IDO protein is detected after treatment with these exogenous factors or with supernatant from activated CD4(+) T cells. We, however, report weak or absent enzymatic activity from these IDO-expressing cells, as assessed by tryptophan consumption. We conclude that IDO may not be a counter-regulatory mechanism utilized by B lymphocytes to down-regulate immune responses, although its expression is inducible.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • B-Lymphocytes / enzymology*
  • B-Lymphocytes / immunology
  • Blotting, Western
  • Cells, Cultured
  • Chromatography, High Pressure Liquid
  • Humans
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / immunology
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / metabolism*
  • Lymphocyte Activation / immunology
  • Microscopy, Fluorescence
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*
  • Toll-Like Receptors / immunology
  • Toll-Like Receptors / metabolism*


  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • Toll-Like Receptors