PT - JOURNAL ARTICLE AU - Courtney E. W. Sulentic AU - Michael P. Holsapple AU - Norbert E. Kaminski TI - Aryl Hydrocarbon Receptor-Dependent Suppression by 2,3,7,8-Tetrachlorodibenzo-<em>p</em>-dioxin of IgM Secretion in Activated B Cells AID - 10.1124/mol.53.4.623 DP - 1998 Apr 01 TA - Molecular Pharmacology PG - 623--629 VI - 53 IP - 4 4099 - http://molpharm.aspetjournals.org/content/53/4/623.short 4100 - http://molpharm.aspetjournals.org/content/53/4/623.full SO - Mol Pharmacol1998 Apr 01; 53 AB - 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.