Milstein C
MRC Laboratory of Molecular Biology, MRC Centre, Hills Road, Cambridge CB2 2QH, United Kingdom.
Bioessays. 1999 Nov;21(11):966-73. doi: 10.1002/(SICI)1521-1878(199911)21:11<966::AID-BIES9>3.0.CO;2-Z.
In this narrative, I describe how my interest in the nature and origin of antibody diversity led me to tackle the problem by using somatic cell genetic techniques. The first hybridoma (an immortal antibody-secreting cell line derived by fusion of a short-lived lymphocyte and a myeloma cell line) was an offshoot of this approach. Although not intended for such purposes, it soon became obvious that this invention had widespread potential in basic research and industry. Indeed, the technique opened new inroads into the study of complex biological substances and became the method of choice to define new differentiation markers. Hybridomas also allowed us to dissect the immune response to a simple antigen and to demonstrate the critical role of somatic mutations in the generation of high affinity antibodies. Now, monoclonal antibodies can be derived and manipulated in vitro, leading to important new developments in therapeutic applications. BioEssays 1999;21:966-973.
在这篇叙述中,我描述了我对抗体多样性的本质和起源的兴趣是如何促使我运用体细胞遗传学技术来解决这个问题的。首个杂交瘤(一种通过短命淋巴细胞与骨髓瘤细胞系融合产生的永生性抗体分泌细胞系)就是这种方法的一个分支产物。尽管并非出于此类目的,但很快就显而易见,这项发明在基础研究和工业领域具有广泛的潜力。事实上,这项技术为研究复杂生物物质开辟了新途径,并成为定义新分化标志物的首选方法。杂交瘤还使我们能够剖析针对单一抗原的免疫反应,并证明体细胞突变在产生高亲和力抗体过程中的关键作用。如今,单克隆抗体能够在体外获得并进行操控,从而在治疗应用方面带来了重要的新进展。《生物论文》1999年;21卷:966 - 973页 。