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 bin ding protein. Although no biologic role for AHR has been elucidated, it med iates the immunotoxicity of xenobiotics such as 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD), and its targeted inactivation produces abnormal immune sys tem development. While investigators have demonstrated AHR's involvement in TCDD-induced B lymphocyte functional alterations, little is known about th e 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 nonhematopoieti c elements and, (3) whether TCDD alters this process. Radiation chimeras we re produced that were AHR positive (Ahr+/+) or negative (Ahr-/-) in either their nonhematopoietic or hematopoietic elements, or both. Marrow cells wer e 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+/+ an imals, (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) A HR is required in both hematopoietic and stromal elements for maintenance o f B cell subset maturation profiles. (C) 2000 Academic Press.