The long term objective for this research is to determine whether the presence of a potent immunotoxic compound, 2,3,7,8-tetrachlorodibenzo-rho- dioxin (TCDD), in the environment presents a health risk to humans and other species. The main goal of the proposed study is to assess the effect of this compound on the B lymphocyte component of the immune system, using a TCDD-sensitive, C57B1/6-Ah(bb) mouse model. Primary specific aims are to address the effect TCDD has on development and maturation of the bone marrow B-2 lymphocytes using flow cytometric analysis of changes in markers specific for this cell type. Flow cytometry will also be used to ascertain whether peritoneal B-1a lymphocytes (a distinct lineage from the B-2 cells) are sensitive to this toxic compound. Determination of whether the effect of TCDD on B lymphocytes segregates with the A h receptor ( specific for halogenated aromatic hydrocarbons) will be accomplished using a congenic strain of mouse which is less sensitive to TCDD (C57B1/6-A h dd). To assess to possibility of a direct effect of TCDD on B cells, both lineages will be evaluated for the presence and activation state of the A h receptor using immunocytochemical procedures. Assessment of a possible indirect role for TCDD will be made by determination of the presence and activation state of A h receptors in bone marrow and peritoneal stromal cells using immunohistochemical techniques. Receptor activation will also be confirmed using the gel retardation assay on nuclear lysates.
