Elucidation of cellular targets responsible for tetrachlorodibenzo-p-dioxin (TCDD)-induced suppression of antibody responses: I. The role of the B lymphocyte.

The objective of these studies was to identify the primary cellular target(s) responsible for TCDD (tetrachlorodibenzo-p-dioxin)-induced suppression of antibody production. Responses to T-independent and T-dependent antigens (administered in vivo or directly to splenic culture) were suppressed in a dose-related fashion in female B6C3F1 mice dosed for 5 consecutive days with 0.1, 1.0 and 10.0 micrograms/kg of 2,3,7,8-TCDD. When nonadherent (B and T) and adherent (macrophage) cells from vehicle- and TCDD-treated mice were combined in various combinations and immunized with either DNP-Ficoll (T-independent) or sRBCs (T-dependent), it was demonstrated that nonadherent cells, but not adherent cells, were functionally affected by TCDD. Similarly, as various combinations of B + macrophage and T + macrophage populations were immunized with sRBCs, the B cell was shown to be the primary target. Using LPS as the stimulus, an inhibition of the antibody response with no effect on the mitogenic response further indicated that the primary target of the TCDD-induced suppression of IgM antibody production is the B lymphocyte at the level of cell differentiation.