Yousaf N, Howard J C, Williams B D
Department of Rheumatology, University Hospital of Wales, Babraham, Cambridge.
Eur J Immunol. 1991 Apr;21(4):943-50. doi: 10.1002/eji.1830210413.
The studies described in this report were designed to investigate factors that could influence the behavior of erythrocytes following their interaction with monoclonal antibodies (mAb) in a fully homologous experimental opsonization system in vivo. The clearance profiles and tissue distribution of target erythrocytes were examined in both normal and decomplemented rats preinjected with rat IgG2a or IgG2b mAb directed against the same or different sites on RT1Aa, the classical class I major histocompatibility complex antigen of the DA rat. Complement played a major role in augmenting the clearance and promoting hepatic sequestration of target erythrocytes in rats preinjected with IgG2a mAb directed against the S site. In contrast, an intact complement system was not an essential requirement for erythrocyte clearance when S site-specific IgG2b mAb were used. With each antibody tested, (DA x PVG)F1 cells, expressing about half as much antigen, were removed significantly slower than DA erythrocytes, this finding being more pronounced when the animals had been preinjected with mAb of the IgG2a isotype. A comparison of the tissue distribution of DA and (DA x PVG)F1 erythrocytes indicated that hepatic uptake was greater for target cells expressing higher antigen density. A considerable degree of heterogeneity was observed in the in vivo behavior of the target erythrocytes with three groups of IgG2b mAb that recognized different sites on the class I molecule. The S site-specific IgG2b mAb were much more efficient in the hepatic Fc receptor-mediated clearance system than were the P site-directed mAb of the same subclass. Our results suggest that antibody specificity may also be a contributory factor, in addition to antibody isotype and target cell antigen density, in determining the fate of target cells in vivo.
本报告中描述的研究旨在调查在体内完全同源的实验性调理系统中，红细胞与单克隆抗体（mAb）相互作用后可能影响其行为的因素。在预先注射针对DA大鼠经典I类主要组织相容性复合体抗原RT1Aa上相同或不同位点的大鼠IgG2a或IgG2b单克隆抗体的正常和去补体大鼠中，检查了靶红细胞的清除曲线和组织分布。补体在增强预先注射针对S位点的IgG2a单克隆抗体的大鼠中靶红细胞的清除和促进肝脏滞留方面起主要作用。相比之下，当使用S位点特异性IgG2b单克隆抗体时，完整的补体系统不是红细胞清除的必要条件。对于所测试的每种抗体，表达约一半抗原量的（DA×PVG）F1细胞的清除速度明显慢于DA红细胞，当动物预先注射IgG2a同种型的单克隆抗体时，这一发现更为明显。对DA和（DA×PVG）F1红细胞组织分布的比较表明，表达较高抗原密度的靶细胞肝脏摄取量更大。在识别I类分子上不同位点的三组IgG2b单克隆抗体的靶红细胞体内行为中观察到相当程度的异质性。S位点特异性IgG2b单克隆抗体在肝脏Fc受体介导的清除系统中比相同亚类的P位点导向单克隆抗体更有效。我们的结果表明，除了抗体同种型和靶细胞抗原密度外，抗体特异性也可能是决定体内靶细胞命运的一个促成因素。
