Aryl Hydrocarbon Receptor-Dependent Suppression by 2,3,7,8-Tetrachlorodibenzo-p-dioxin of IgM Secretion in Activated B Cells
- Department of Pharmacology and Toxicology and Department of Pathology, Michigan State University, East Lansing, Michigan 48824
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.
Footnotes
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Send reprint requests to: Dr. Norbert E. Kaminski, Dept. of Pharmacology & Toxicology, B330 Life Sciences Bldg., Michigan State University, East Lansing, MI 48824.
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↵1 Current affiliation: Dow Chemical Company, Midland, MI 48674.
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This work was supported in part by funds from National Institute of Environmental Health Sciences Grant ES02520.
- Abbreviations:
- HAH
- halogenated aromatic hydrocarbon
- TCDD
- 2,3,7,8-tetrachlorodibenzo-p-dioxin
- AhR
- aryl hydrocarbon receptor
- ARNT
- aryl hydrocarbon receptor nuclear translocator
- DRE
- dioxin-responsive enhancer
- LD50
- 50% of lethal dose
- RT
- reverse transcriptase
- PCR
- polymerase chain reaction
- LPS
- lipopolysaccharide
- ELISA
- enzyme-linked immunosorbent assay
- BSAP
- B cell-specific activator protein
- PAGE
- polyacrylamide gel electrophoresis
- DMSO
- dimethylsulfoxide
- HEPES
- 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid
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- Received October 6, 1997.
- Accepted December 22, 1997.
- The American Society for Pharmacology and Experimental Therapeutics
