ARYL-HYDROCARBON RECEPTOR-DEPENDENT SUPPRESSION BY 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN OF IGM SECRETION IN ACTIVATED B-CELLS

The immune system has been identified as a sensitive target for the to xic effects produced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Fu rthermore, the B cell has been identified as a sensitive cellular targ et of TCDD by previous cell-type fractionation studies from this labor atory. The mechanism responsible for the immunotoxic effects produced by TCDD is unclear; however, many of the biological effects of TCDD ar e thought to be mediated by the aryl hydrocarbon receptor (AhR). Here, we describe two B cell lines that differ considerably in their expres sion of the AhR and in their sensitivity to TCDD. Our results demonstr ated 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 de tected by reverse transcriptase-polymerase chain reaction in the BCL-1 cells. The AhR nuclear translocator (ARNT) protein was highly express ed in both cell lines. In addition, the AhR and ARNT are functional in CH12.LX cells as demonstrated by TCDD-induced CYPIA1 induction. TCDD did not induce CYP1A1 in BCL-1 cells. Furthermore, TCDD treatment resu lted 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 rol e for the AhR in the inhibition of B cell effector function. LPS-induc ed differentiation of the CH12.LX cells also resulted in a marked indu ction of Ahr expression which was not induced in LPS-stimulated BCL-1 cells. These studies have implicated the AhR as a critical factor in T CDD-induced inhibition of IgM secretion and have demonstrated an induc tion of AhR gene and protein expression after B cell activation.