Large, activated B cells are the primary B-cell target of 8-bromoguanosine and 8-mercaptoguanosine.
Previous studies have documented the ability of 8-bromoguanosine (8-BrGuo) and 8-mercaptoguanosine (8-MGuo) to induce polyclonal proliferation and differentiation of B cells from a variety of mouse strains. In the present study, we have defined the cellular target of this mitogenic activity. Using B cells fractionated according to size, we have found that large B cells are responsive to 8-BrGuo- and 8-MGuo-induced proliferation and differentiation whereas small, resting B cells are relatively unresponsive to these compounds. Addition of splenic adherent cells to the small B-cell fraction partially restored the proliferative but not the differentiative responses to 8-BrGuo and 8-MGuo. Although small B cells alone did not proliferate or differentiate in response to 8-BrGuo and 8-MGuo, cell surface expression of Ia antigens increased following incubation with these compounds. Thus, the biological activity of 8-BrGuo and 8-MGuo appears to be dictated by the cell type upon which it is acting. Small B cells are activated as evidenced by increased levels of surface Ia whereas large B cells are not only activated but are also induced to proliferate and differentiate.
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D000917:Antibody Formation; D000954:Antigens, Surface / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D006151:Guanosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects*; D008264:Macrophages / Q000502:physiology; D051379:Mice; D009113:Muramidase / Q000276:immunology; D011947:Receptors, Antigen, B-Cell / Q000502:physiology; D013154:Spleen / Q000166:cytology; D013872:Thionucleosides / Q000494:pharmacology*
D000888:Antibodies, Anti-Idiotypic; D000954:Antigens, Surface; D000949:Histocompatibility Antigens Class II; D011947:Receptors, Antigen, B-Cell; D013872:Thionucleosides; D006151:Guanosine; C035169:8-bromoguanosine; C037031:8-thioguanosine; D009113:Muramidase