Milstein C, Galfre G, Secher D S, Springer T
Ciba Found Symp. 1979(66):251-76. doi: 10.1002/9780470720486.ch11.
Antibody chains are encoded in three gene clusters containing genes for the variable and constant regions. V and C genes are separated in germ line and during differentiation a rearrangement takes place. But even after this rearrangement the V and C coding sequences are not contiguous. A final splicing must take place in committed cells between the transcription of a discontinuous V-and C-region DNA and the expression of a continuous mRNA coding for an antibody chain. Analysis by cell fusion indicates that the splicing is cis. When two antibody-producing cell lines are fused, the resulting hybrids express the two antibodies that characterize the parental lines. Permanent cell lines producing antibody of predefined specificity have now been derived in this way. Spleen cells from hyperimmunized donors are fused with myeloma cells and a proportion of the hybrids that are established synthesize and secrete antibodies directed against the immunogen. The heterogeneous cell population can be cloned and propagated. This is a potent way of producing monospecific antibodies to complex antigens such as cell membranes and transplantation antigens. Monoclonal xenogeneic antibodies to rat cell-surface membranes have proved very valuable for characterizing and separating rat lymphocyte subpopulations. In more recent experiments, monoclonal xenogeneic antibodies to mouse and human cell-surface antigens have also been produced which permit the characterization of the hitherto undescribed differentiation antigens.
抗体链由三个基因簇编码，这些基因簇包含可变区和恒定区的基因。V基因和C基因在种系中是分开的，在分化过程中会发生重排。但即使经过这种重排，V和C编码序列也不相邻。在终末分化细胞中，不连续的V区和C区DNA转录与编码抗体链的连续mRNA表达之间必须进行最终剪接。细胞融合分析表明这种剪接是顺式的。当两个产生抗体的细胞系融合时，产生的杂种细胞表达代表亲代细胞系特征的两种抗体。现在已经通过这种方式获得了产生预定义特异性抗体的永久细胞系。将经超免疫供体的脾细胞与骨髓瘤细胞融合，一部分建立起来的杂种细胞合成并分泌针对免疫原的抗体。可以对异质细胞群体进行克隆和繁殖。这是一种生产针对复杂抗原（如细胞膜和移植抗原）的单特异性抗体的有效方法。事实证明，针对大鼠细胞表面膜的单克隆异种抗体对于鉴定和分离大鼠淋巴细胞亚群非常有价值。在最近的实验中，还产生了针对小鼠和人类细胞表面抗原的单克隆异种抗体，这些抗体可以鉴定迄今未描述的分化抗原。
