Larrick J W, Fry K E
Genelabs Inc., Redwood City, CA 94063.
Hum Antibodies Hybridomas. 1991 Oct;2(4):172-89.
Many fundamental advances in our understanding of the structure and function of eukaryotic genes were derived from the study of antibody genes. Examples include mRNA splicing and rearrangement to generate antibody diversity. The capacity to immortalize an individual B cell using cell fusion permitted the generation of monoclonal antibodies. Monoclonal antibodies have had wide application in many fields of the life sciences and beyond. Recent advances permitting manipulation of antibody genes using recombinant DNA techniques offer many advantages over conventional somatic cell hybridization techniques. Rodent monoclonals can be "humanized" and antibody isotype readily changed. Grafting of the complementarity determining regions from rodent to human framework regions demonstrated the importance of these hypervariable portions of the immunoglobulin to the integrity of the antibody combining site. Recombinant monoclonal antibodies (rMAb) or fragments thereof have been successfully produced in both prokaryotic and eukaryotic hosts at levels equal to those produced by hybridomas. Successful efforts to express rMAbs in plants and other large capacity systems suggest that rMAbs can be produced inexpensively. Use of antibody catalysis and antibodies mimicking various receptors or ligands have numerous applications. Technology developed to immortalize the heavy and light chain repertoire permits the generation in vitro of recombinatorial libraries of antibodies. The capacity to artificially generate high-affinity antibodies in vitro using the methods of recombinant DNA technology has enormous pharmaceutical and industrial potential.
我们对真核基因结构与功能的许多重要认识进展都源自对抗体基因的研究。例如，mRNA剪接和重排以产生抗体多样性。利用细胞融合使单个B细胞永生化的能力促成了单克隆抗体的产生。单克隆抗体在生命科学及其他众多领域都有广泛应用。最近，利用重组DNA技术对抗体基因进行操作取得的进展，相比传统的体细胞杂交技术具有诸多优势。啮齿动物单克隆抗体可以“人源化”，抗体亚型也易于改变。将啮齿动物的互补决定区嫁接到人框架区，证明了免疫球蛋白这些高变部分对抗体结合位点完整性的重要性。重组单克隆抗体（rMAb）或其片段已在原核和真核宿主中成功生产，产量与杂交瘤相当。在植物和其他大容量系统中成功表达rMAb的尝试表明，rMAb可以低成本生产。抗体催化以及模拟各种受体或配体的抗体的应用十分广泛。使重链和轻链库永生化的技术能够在体外产生抗体重组文库。利用重组DNA技术在体外人工产生高亲和力抗体的能力具有巨大的制药和工业潜力。
