title: Relationship between Ah receptor-mediated polychlorinated biphenyl (PCB)-induced humoral immunosuppression and thymic atrophy.
abstract: Thymic atrophy and humoral immunosuppression by certain polychlorinated biphenyls is associated with the aromatic hydrocarbon (Ah) receptor in mice. We examined the relationship between these two toxic effects. 3,3',4,4'-Tetrachlorobiphenyl (TCB), which causes immunosuppression and thymic atrophy, and 2,3,3',4,4',5-hexachlorobiphenyl, which causes immunosuppression without thymic atrophy, were administered i.p. to C57BL/6 mice at 0, 35 and 350 mumol/kg b.wt. 2 days before i.v. immunization with 10 micrograms of Escherichia coli lipopolysaccharide. Both congeners caused significant suppression of the day 4 anti-lipopolysaccharide plaque-forming cell response/spleen (less than or equal to 46% of control). TCB (350 mumol/kg) was also administered 2 days before either a primary or secondary i.p. immunization with sheep erythrocytes. TCB treatment before primary immunization had no effects on the day 5 secondary response, whereas treatment before the secondary immunization significantly inhibited both day 5 immunoglobulin M and immunoglobulin G plaque-forming cells (less than 10 and less than 2% of control, respectively) and decreased serum antibody. TCB administered either 8 or 2 days before or 2 or 4 days after immunization with sheep erythrocytes demonstrated that significant suppression of both plaque-forming cells and serum antibody could occur without thymic atrophy. Immunity was most impaired when TCB was given 2 days before immunization. These results demonstrate that thymic atrophy does not always accompany the severe immunosuppression caused by Ah receptor ligands and suggests that it may not be a sensitive measure of Ah receptor-mediated immunosuppression. The data also suggests that differentiation of B lymphocytes into antibody producing cells is impaired during Ah receptor-mediated gene activation.
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000187:drug effects*; D001284:Atrophy; D004912:Erythrocytes / Q000276:immunology; D007166:Immunosuppressive Agents / Q000633:toxicity*; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size / Q000187:drug effects; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D018336:Receptors, Aryl Hydrocarbon; D011955:Receptors, Drug / Q000502:physiology*; D012756:Sheep; D013950:Thymus Gland / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D013997:Time Factors
chemical_list: D007166:Immunosuppressive Agents; D008070:Lipopolysaccharides; D018336:Receptors, Aryl Hydrocarbon; D011955:Receptors, Drug; D011078:Polychlorinated Biphenyls