Copyright () by The American Society for Pharmacology and Experimental Therapeutics All rights of reproduction in any form reserved. MOLECULAR PHARMACOLOGY, 29:372-377 Suppression of B Cell Differentiation by 2,3,7,8-

Acute exposure of adult mice to 2,3,7,8-tetrachlorodibenzo-p- gested that this inhibition was mediated by the Ah receptor. As dioxin (TCDD) results in a selective suppression of proliferating previously defined by receptor binding studies in hepatic cytosol, cells of the immune system, including hematopoietic stem cells active congeners were inhibitory, whereas inactive congeners and B cells. Suppression of B cell-mediated or humoral immunity, were without effect. Using lymphocytes from congenic mice in turn, results in altered host resistance to the parasite P/as- which differ only at the Ah locus, it was determined that the modium yoe/ll, a malaria model. Data presented in this study Ah-derived cells were inhibited by TCDD in vitro, whereas the demonstrate a direct effect of TCDD on cultured lymphoctes Ahddderived cells were not. B cell differentiation thus provides a resulting in a selective inhibition of the differentiation of B cells valuable model for understanding TCDD toxicity as well as the into antibody-secreting cells. A structure-activity study sug- role of the Ah receptor in growth and differentiation. TCDD is a prototype chemical for the halogenated aromatic responsive C57BL/6 mice, whereas lymphoproliferative re-hydrocarbons, an important class of environmental contami- sponses and the ability to mediate graft-versus-host reactions nants. In spite of wide variations in species sensitivity and were not affected (6). Suppression of the humoral immune responses to TCDD, there are common manifestations of tox- response was subsequently shown to correlate with the suscep-icity, as reviewed recently by Poland and Knutson (1). These tibility of the strain of mouse to induction of AHH using include wasting syndrome, thymic atrophy, hepatomegaly, C57BL6, DBA/2, B6D2F1, and backcrosses (7). More recently