Journal Article

Bone Marrow Stromal-B Cell Interactions in Polycyclic Aromatic Hydrocarbon-Induced Pro/Pre-B Cell Apoptosis

Lenka L. Allan, Koren K. Mann, Raymond A. Matulka, Heui-Young Ryu, Jennifer J. Schlezinger and David H. Sherr

in Toxicological Sciences

Volume 76, issue 2, pages 357-365
Published in print December 2003 | ISSN: 1096-6080
Published online December 2003 | e-ISSN: 1096-0929 | DOI: http://dx.doi.org/10.1093/toxsci/kfg239
Bone Marrow Stromal-B Cell Interactions in Polycyclic Aromatic Hydrocarbon-Induced Pro/Pre-B Cell Apoptosis

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Environmental polycyclic aromatic hydrocarbons (PAH) and related halogenated hydrocarbons are immunotoxic in a variety of systems. In a model system of B lymphopoiesis, PAH exposure rapidly induces apoptosis in CD43 pre-B and CD43+ pro/pre-B cells. Apoptosis induction by 7,12-dimethylbenzo[a]anthracene (DMBA) is dependent upon AhR+ bone marrow stromal cells and likely involves DMBA metabolism within the stromal cell. However, it is not known if PAH-treated stromal cells release free metabolites or soluble factors that may directly induce B cell death or if the effector death signal is delivered by stromal cell-B cell contact. Here, we demonstrate that supernatants from DMBA-treated bone marrow stromal cells contain an activity capable of inducing apoptosis in pro/pre-B cells cocultured with stromal cells. This activity (1) is not produced when stromal cells are cotreated with DMBA and α-naphthoflavone (α-NF), an aryl hydrocarbon receptor (AhR) and cytochrome P-450 inhibitor, (2) is ≥ 50 kDa, (3) is trypsin and heat sensitive, and (4) is dependent on AhR+ stromal cells, which in turn deliver the effector death signal to pro/pre-B cells. The results (1) argue against a role for a soluble, stromal cell-derived cytokine as the effector of PAH-induced pro/pre-B cell death, (2) exclude the possibility of a free metabolite acting directly on AhR pro/pre-B cell targets, and (3) suggest the elaboration by stromal cells of a relatively stable, DMBA metabolite-protein complex capable of acting on other stromal cells at some distance. Collectively, these studies suggest that, while stromal cell products, e.g., metabolite-protein complexes, may affect the function of distant stromal cells, the effector death signal delivered by stromal cells to bone marrow B cells is mediated by cell–cell contact.

Keywords: polycyclic aromatic hydrocarbon; B cell apoptosis; stromal cells

Journal Article.  6878 words.  Illustrated.

Subjects: Medical Toxicology ; Toxicology (Non-medical)

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