Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on humoral immunity: II. B cell activation.

Previous reports have indicated similarities in the actions of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and the polyclonal B cell activator Staphylococcus aureus Cowan Strain I (SAC) on the in vitro T-dependent antibody response to SRBC. This finding has suggested that B cell activation is likely to be an important component in the direct effects of TCDD on lymphocyte function. In the current investigation, various techniques were employed to determine whether TCDD could cause the activation of splenic-derived dense resting B cells in the absence of antigen and to determine if the modulatory effect of serum-derived growth factors is the result of a direct action on the B lymphocyte. TCDD (30 and 60 nM) caused an increase in proliferation of dense resting B cells at both 72 and 96 h following addition. This action of TCDD was demonstrated to possess a serum dependency that was based on the lot of serum in which the cells were cultured. Under similar conditions, TCDD (30 nM) stimulated an increase in total IgM secretion as measured on day 7 of culture. A similar profile of activity was observed in vivo, where splenic-derived dense resting B cells from animals treated with 1 microgram/kg TCDD for 5 days, but unsensitized to SRBC, demonstrated a 10-fold increase in proliferation on day 3 of culture which likewise occurred in a serum dependent manner. In addition, we observed that mice treated with 1 microgram/kg TCDD for 5 days and sensitized with SRBCs, sustained a complete loss in their splenic-derived dense B cell populations (day 4 after sensitization). The loss of this B cell population is indicative of a movement of these cells into a blastogenic state of activation and is not observed in matched corn oil-treated controls. These findings support our previous observations and give evidence that TCDD is capable of causing the direct activation of resting B cells. This activation is dependent on the type of serum present during in vitro culture and appears to be intensified in the presence of antigen in vivo.