title: Primary cellular target responsible for dimethylnitrosamine-induced immunosuppression in the mouse.
abstract: The present studies were undertaken to identify the cellular targets responsible for immunosuppression by dimethylnitrosamine (DMN). The in vitro antibody responses of splenocytes from B6C3F1 mice exposed to 6 mg/kg DMN for 7 days to the T cell-independent antigen dinitrophenyl-Ficoll and the T cell-dependent antigen sheep erythrocytes were used for separation and reconstitution studies. The antibody-forming cell response of spleen cells from DMN-treated mice to the T-independent and T-dependent antigens was suppressed by 72% and 61%, respectively, when compared to vehicle controls. Whole spleen suspensions were fractionated into nonadherent populations by plastic adherence and Sephadex G-10 depletion of macrophages. Adherent antigen-presenting cells were obtained by incubating spleen suspensions in culture wells and removing nonadherent cells after 3 h. By combining vehicle and DMN nonadherent and adherent populations it was demonstrated that the population most affected by DMN exposure in both the sheep erythrocyte and dinitrophenyl-Ficoll responses was the nonadherent population. The lack of T cell dependence of the dinitrophenyl-Ficoll response was verified by elimination of T cells from whole spleen suspensions by monoclonal anti-thy 1.2 antibody plus complement treatment. These results indicated the B cell from DMN-treated mice as the splenic cell type responsible for suppressed antibody-forming cell responses to dinitrophenyl-Ficoll. B cells, T cells (prepared by cytotoxic elimination of B cells using anti-immunoglobulins) and adherent antigen-presenting cells (macrophages) from vehicle- and DMN-treated mice were fractionated and recombined and immunized with sheep erythrocytes (requires B cell, T cell, and macrophage cooperation). While splenic macrophages from DMN-treated mice supported control responses, T-helper activity was slightly reduced and B cell function was especially impaired. The conclusion that T cell function was less suppressed was supported by control responses of DMN-treated mice to concanavalin A but reduced responsiveness to lipopolysaccharide under conditions of limiting cell densities. These studies indicate that the primary cellular target of DMN exposure resulting in suppressed antibody responses is the B lymphocyte.
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000187:drug effects; D001402:B-Lymphocytes / Q000187:drug effects*; D002448:Cell Adhesion / Q000187:drug effects; D003208:Concanavalin A / Q000276:immunology; D004128:Dimethylnitrosamine / Q000494:pharmacology*; D004912:Erythrocytes / Q000276:immunology; D005260:Female; D005362:Ficoll / Q000031:analogs & derivatives / Q000276:immunology; D007166:Immunosuppressive Agents; D008264:Macrophages / Q000276:immunology; D051379:Mice; D012756:Sheep / Q000276:immunology; D013154:Spleen / Q000187:drug effects / Q000276:immunology*; D013601:T-Lymphocytes / Q000187:drug effects*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
chemical_list: C031007:DNP-Ficoll; D007166:Immunosuppressive Agents; D003208:Concanavalin A; D005362:Ficoll; D004128:Dimethylnitrosamine