Lees A, Morris S C, Thyphronitis G, Holmes J M, Inman J K, Finkelman F D
Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814-4799.
J Immunol. 1990 Dec 1;145(11):3594-600.
Injection of mice with goat anti-mouse IgD antibody stimulates a large IgG1 anti-goat IgG antibody response, as well as polyclonal IgG1 production. To determine if this phenomenon could be used to induce large antibody responses to other Ag, covalent conjugates were produced between BSA or other Ag and H delta a/1, a mAb specific for IgD of the a allotype, and between BSA and AF3.33, a mAb specific for IgD of the b allotype. Injection of H delta a/1-BSA into BALB/c mice, which express Ig of the a allotype, or into (BALB/c x CB20)F1 mice (a x b allotype heterozygotes) induced IgG1 anti-BSA antibody responses that peaked 8 to 9 days after injection, and were more than 1000 times larger than those induced by injection of BSA alone, and 100 times larger than those induced by injecting unconjugated BSA plus H delta a/1. H delta a/1-BSA was no more immunogenic than unconjugated BSA when injected into CB20 mice, which express Ig of the b allotype, while AF3.33-BSA greatly enhanced anti-BSA antibody production in CB20, but not in BALB/c mice. Mice serially immunized with three different Ag conjugated to H delta a/1 made large antibody responses to all three Ag, provided that the mouse strain used did not recognize allotypic determinants on H delta a/1 as foreign and produce a neutralizing antibody response. Intravenous and s.c. routes of inoculation produced responses of similar magnitude and relatively low variability; responses to footpad or intramuscular inoculation were more variable, and i.p. inoculation induced smaller responses. Injection of BALB/c mice i.v. with 100 micrograms of H delta a/1-BSA induced an IgG1 anti-BSA response of 5.6 mg/ml, which was approximately 70% of the total IgG1 response. Anti-BSA responses to 30 micrograms of conjugate or less were much smaller, but could be considerably enhanced by adding unconjugated H delta a/1 to the inoculum. This system will be useful for the rapid stimulation of large antibody responses to biologically important Ag, and for investigating mechanisms of Ag processing and B and T cell activation.
给小鼠注射山羊抗小鼠IgD抗体可刺激产生大量的IgG1抗山羊IgG抗体反应以及多克隆IgG1的产生。为了确定这种现象是否可用于诱导对其他抗原的大量抗体反应，制备了牛血清白蛋白（BSA）或其他抗原与Hδa/1（一种针对a同种异型IgD的单克隆抗体）之间的共价缀合物，以及BSA与AF3.33（一种针对b同种异型IgD的单克隆抗体）之间的共价缀合物。将Hδa/1-BSA注射到表达a同种异型Ig的BALB/c小鼠或（BALB/c×CB20）F1小鼠（a×b同种异型杂合子）中，诱导产生的IgG1抗BSA抗体反应在注射后8至9天达到峰值，比单独注射BSA诱导的反应大1000倍以上，比注射未缀合的BSA加Hδa/1诱导的反应大100倍。当将Hδa/1-BSA注射到表达b同种异型Ig的CB20小鼠中时，其免疫原性并不比未缀合的BSA更强，而AF3.33-BSA则大大增强了CB20小鼠中抗BSA抗体产生，但在BALB/c小鼠中则不然。用与Hδa/1缀合的三种不同抗原对小鼠进行连续免疫，可使小鼠对所有三种抗原都产生大量抗体反应，前提是所用小鼠品系不将Hδa/1上的同种异型决定簇识别为外来物并产生中和抗体反应。静脉内和皮下接种途径产生的反应幅度相似且变异性相对较低；对足垫或肌肉内接种的反应变异性更大，而腹腔内接种诱导的反应较小。给BALB/c小鼠静脉内注射100微克Hδa/1-BSA可诱导产生5.6毫克/毫升的IgG1抗BSA反应，约占总IgG1反应的70%。对30微克或更少缀合物的抗BSA反应要小得多，但通过在接种物中添加未缀合的Hδa/1可使其显著增强。该系统将有助于快速刺激对生物学上重要抗原的大量抗体反应，并用于研究抗原加工以及B和T细胞活化的机制。
