title: Close proximity, but not VLA-4-dependent adherence between pre-B cells and bone marrow stromal cells, is required for DMBA-induced apoptosis of pre-B cells in vitro.
abstract: We have previously reported that 7,12-dimethylbenz[a]anthracene (DMBA) induced apoptosis in precursor B lymphocytes (pre-B cells) only when they were co-cultured with bone marrow stromal (BMS) cells. The goal of this research was to determine whether this process was dependent on the adherence of the pre-B cells and stromal cells. Conditioned media from DMBA-treated BMS cells induced apoptosis in pre-B cells, but only when the pre-B cells were co-cultured with stromal cells. This result suggested that stromal cells may release a soluble factor that initiates apoptosis, but their presence was still required for apoptosis. When the stromal cells and pre-B cells were separated with a membrane filter insert, DMBA-induced apoptosis of the pre-B cells was blocked suggesting that contact with or close proximity to stromal cells was required for apoptosis. The addition of an anti-VLA-4 Mab disrupted adherence of pre-B cells to the stromal cell monolayer, but did not diminish the numbers of apoptotic pre-B cells. The results of this study support the hypothesis stromal cells and pre-B cells must be in close proximity for apoptosis to occur, but direct interaction via VLA-4 and VCAM-1 is unlikely to be required for this response.
authors.affiliation: Department of Patholobiolgical Sciences, University of Wisconsin-Madison, 2015 Linden Drive West, Madison, WI 53706, USA.
authors.forename: Alice S
authors.initials: AS
authors.lastname: Yuroff
authors.forename: Colin R
authors.initials: CR
authors.lastname: Jefcoate
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Czuprynski
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001402:B-Lymphocytes / Q000502:physiology*; D001551:Benz(a)Anthracenes / Q000633:toxicity*; D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology*; D002448:Cell Adhesion; D002460:Cell Line; D004785:Environmental Pollutants / Q000633:toxicity; D039041:Integrin alpha4beta1 / Q000502:physiology*; D051379:Mice; D051381:Rats; D013234:Stem Cells / Q000502:physiology*; D017154:Stromal Cells / Q000502:physiology; D019010:Vascular Cell Adhesion Molecule-1 / Q000502:physiology
chemical_list: D001551:Benz(a)Anthracenes; D004785:Environmental Pollutants; D039041:Integrin alpha4beta1; D019010:Vascular Cell Adhesion Molecule-1; C046810:7,12-dihydroxymethylbenz(a)anthracene