Aryl hydrocarbon receptor-dependent suppression by 2,3,7, 8-tetrachlorodibenzo-p-dioxin of IgM secretion in activated B cells

Mol Pharmacol. 1998 Apr;53(4):623-9.

Abstract

The immune system has been identified as a sensitive target for the toxic effects produced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Furthermore, the B cell has been identified as a sensitive cellular target of TCDD by previous cell-type fractionation studies from this laboratory. The mechanism responsible for the immunotoxic effects produced by TCDD is unclear; however, many of the biological effects of TCDD are thought to be mediated by the aryl hydrocarbon receptor (AhR). Here, we describe two B cell lines that differ considerably in their expression of the AhR and in their sensitivity to TCDD. Our results demonstrated a marked expression of the AhR protein in the CH12.LX B cell line but not in the BCL-1 B cell line. Transcripts for the AhR were not detected by reverse transcriptase-polymerase chain reaction in the BCL-1 cells. The AhR nuclear translocator (ARNT) protein was highly expressed in both cell lines. In addition, the AhR and ARNT are functional in CH12.LX cells as demonstrated by TCDD-induced CYP1A1 induction. TCDD did not induce CYP1A1 in BCL-1 cells. Furthermore, TCDD treatment resulted in suppression of lipopolysaccharide (LPS)-induced IgM secretion in CH12.LX cells. Conversely, TCDD-induced inhibition of IgM secretion was not demonstrated in LPS-stimulated BCL-1 cells, implicating a role for the AhR in the inhibition of B cell effector function. LPS-induced differentiation of the CH12.LX cells also resulted in a marked induction of Ahr expression which was not induced in LPS-stimulated BCL-1 cells. These studies have implicated the AhR as a critical factor in TCDD-induced inhibition of IgM secretion and have demonstrated an induction of AhR gene and protein expression after B cell activation.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Aryl Hydrocarbon Receptor Nuclear Translocator
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism*
  • Carcinoma, Hepatocellular
  • Cell Differentiation / drug effects
  • Cell Differentiation / immunology
  • DNA-Binding Proteins*
  • Gene Expression Regulation / drug effects
  • Immunoglobulin M / metabolism*
  • Immunosuppressive Agents / pharmacology*
  • Lipopolysaccharides / pharmacology
  • Lymphocyte Activation / drug effects*
  • Lymphoma, B-Cell / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Polychlorinated Dibenzodioxins / metabolism
  • Polychlorinated Dibenzodioxins / pharmacology*
  • Receptors, Aryl Hydrocarbon / biosynthesis
  • Receptors, Aryl Hydrocarbon / drug effects
  • Receptors, Aryl Hydrocarbon / physiology*
  • Transcription Factors / biosynthesis
  • Transcription, Genetic / drug effects
  • Tumor Cells, Cultured

Substances

  • Arnt protein, mouse
  • DNA-Binding Proteins
  • Immunoglobulin M
  • Immunosuppressive Agents
  • Lipopolysaccharides
  • Polychlorinated Dibenzodioxins
  • Receptors, Aryl Hydrocarbon
  • Transcription Factors
  • Aryl Hydrocarbon Receptor Nuclear Translocator