Ah receptor mediated suppression of the antibody response in mice is primarily dependent on the Ah phenotype of lymphoid tissue
Halogenated aromatic hydrocarbons act through the aromatic hydrocarbon (Ah) receptor in mice to produce a series of toxic effects of the immune system. The receptor protein is a product of the Ah gene locus. Ah responsive (Ahb/Ahb) mice express a high affinity receptor in both lymphoid and nonlymphoid tissues whereas nonresponsive Ahd/Ahd mice express a poor affinity receptor. To determine the role of the Ah receptor of lymphoid tissue relative to that of nonlymphoid tissue in the induction of immune impairment, bone marrow was used to reconstitute lethally irradiated mice of the same or opposite Ah phenotype. All mice were given 3,3',4,4'-tetrachlorobiphenyl (35 and 350 mumol/kg) ip 2 days before immunization with sheep erythrocytes (SRBC). The immune response to this T dependent antigen and organ weights were determined 5 or 7 days later in normal or chimeric mice, respectively. Monoclonal Lyt 1.1 and Lyt 1.2 antibodies were used to establish the origin of the cells which repopulated the chimeric thymuses. The immune responses of both BALB/cBy (Ahb/Ahb) and the BALB/cBy X DBA/2 hybrid, CByD2F1 (Ahb/Ahd), were significantly suppressed but DBA/2 mice were unaffected. The immune responses of chimeric BALB/cBy----BALB/cBy and BALB/cBy----DBA/2 (donor----recipient) mice were also significantly suppressed and thymic atrophy was observed in both cases. The serum anti-SRBC antibody titers of DBA/2----BALB/cBy chimeras were also significantly decreased although not to the same extent as in BALB/cBy----DBA/2 mice. Chimeric DBA/2----DBA/2 mice were not affected. These results indicate that the sensitivity to Ah receptor mediated suppression of the antibody response is primarily determined by the Ah phenotype of the lymphoid tissue.
- Research Organization:
- New York State Department of Health, Albany, NY
- OSTI ID:
- 6927210
- Journal Information:
- Toxicol. Appl. Pharmacol.; (United States), Journal Name: Toxicol. Appl. Pharmacol.; (United States) Vol. 3; ISSN TXAPA
- Country of Publication:
- United States
- Language:
- English
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560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL TISSUES
ANIMALS
ANTIBODIES
ANTIBODY FORMATION
AROMATICS
BODY
BONE MARROW
CHIMERAS
HALOGENATED AROMATIC HYDROCARBONS
HEMATOPOIETIC SYSTEM
IMMUNE REACTIONS
INHIBITION
IRRADIATION
LETHAL IRRADIATION
LYMPHATIC SYSTEM
MAMMALS
MEMBRANE PROTEINS
MICE
MONOCLONAL ANTIBODIES
MOSAICISM
ORGANIC COMPOUNDS
ORGANIC HALOGEN COMPOUNDS
ORGANS
PHENOTYPE
PROTEINS
RADIATION CHIMERAS
RECEPTORS
RETICULOENDOTHELIAL SYSTEM
RODENTS
THYMUS
TISSUES
TOXICITY
TRANSPLANTS
VERTEBRATES