Ill C R, Brehm T, Lydersen B K, Hernandez R, Burnett K G
Department of In Vitro Antibody Production, Hybritech, Inc., San Diego, California 92121.
In Vitro Cell Dev Biol. 1988 May;24(5):413-9. doi: 10.1007/BF02628492.
Studies with Human X Human (H X H), Human X Mouse (H X M), and Mouse X Mouse (M X M) hybridomas have enabled us to define specific factors that affect hybridoma growth in a species-specific manner. Three transferrins and three lipophilic iron chelates have been tested for their ability to support hybridoma proliferation and antibody production. The results of these studies demonstrate that H X H hybridomas do not respond to bovine transferrin a+ concentrations up to 100 micrograms/ml and are approximately 100-fold less responsive to mouse transferrin than to human transferrin. H X M and M X M hybridomas respond equally to human or mouse transferrin but are 100-fold less sensitive to bovine transferrin. An antibody to the human transferrin receptor inhibited the growth-promoting activity of human or mouse transferrin on H X H hybridomas but was ineffective on H X M hybridomas. This demonstrated the functionality of the human transferrin receptor in H X H hybridomas and that human, mouse, and bovine transferrin were interacting through the mouse transferrin receptor in H X M hybridomas. H X H and H X M hybridomas respond similarly to three different iron chelates exhibiting 80 to 110% of the growth response to human transferrin. M X M hybridomas fail to respond to the iron chelates at similar concentrations, suggesting that the human genome present in the other hybridoma species confers a unique ability for utilizing iron when delivered in this form.
对人-人(H×H)、人-小鼠(H×M)和小鼠-小鼠(M×M)杂交瘤的研究,使我们能够确定以物种特异性方式影响杂交瘤生长的特定因素。已测试了三种转铁蛋白和三种亲脂性铁螯合物支持杂交瘤增殖和抗体产生的能力。这些研究结果表明,H×H杂交瘤对浓度高达100微克/毫升的牛转铁蛋白无反应,对小鼠转铁蛋白的反应比对人转铁蛋白的反应低约100倍。H×M和M×M杂交瘤对人或小鼠转铁蛋白的反应相同,但对牛转铁蛋白的敏感性低100倍。一种抗人转铁蛋白受体的抗体抑制了人或小鼠转铁蛋白对H×H杂交瘤的促生长活性,但对H×M杂交瘤无效。这证明了人转铁蛋白受体在H×H杂交瘤中的功能,以及人、小鼠和牛转铁蛋白在H×M杂交瘤中通过小鼠转铁蛋白受体相互作用。H×H和H×M杂交瘤对三种不同铁螯合物的反应相似,对人转铁蛋白的生长反应为80%至110%。M×M杂交瘤在相似浓度下对铁螯合物无反应,这表明存在于其他杂交瘤物种中的人类基因组赋予了以这种形式递送时利用铁的独特能力。