The aryl hydrocarbon receptor has a role in the in vivo maturation of murine bone marrow B lymphocytes and their response to 2,3,7,8-tetrachlorodibenzo-p-dioxin.
The ligand-activated aryl hydrocarbon receptor (AHR) is a cytosolic DNA binding protein. Although no biologic role for AHR has been elucidated, it mediates the immunotoxicity of xenobiotics such as 2, 3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and its targeted inactivation produces abnormal immune system development. While investigators have demonstrated AHR's involvement in TCDD-induced B lymphocyte functional alterations, little is known about the receptor's possible role in early B cell maturation and whether exogenous ligands change this process. The purpose of this study was to determine, (1) whether bone marrow B lymphocyte maturation is affected by AHR presence, (2) if so, its relative importance in hematopoietic and/or nonhematopoietic elements and, (3) whether TCDD alters this process. Radiation chimeras were produced that were AHR positive (Ahr+/+) or negative (Ahr-/-) in either their nonhematopoietic or hematopoietic elements, or both. Marrow cells were analyzed for alterations in B lymphocyte maturation stage cell numbers in both vehicle- and TCDD-treated animals. Our results showed that (1) Ahr-/- animals had significantly higher numbers of pro/pre-B cells than Ahr+/+ animals, (2) TCDD treatment of Ahr+/+ animals produced a decrease in pro/pre-B cell numbers, whereas no effect was observed on Ahr-/- animals, and (3) AHR is required in both hematopoietic and stromal elements for maintenance of B cell subset maturation profiles.
Thurmond
T S
TS
Department of Environmental Medicine, University of Rochester, Rochester, New York 14642, USA.
Staples
J E
JE
Silverstone
A E
AE
Gasiewicz
T A
TA
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects*; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D005434:Flow Cytometry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D018336:Receptors, Aryl Hydrocarbon / Q000502:physiology*
D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon