Milstein, César


César Milstein (1927–2002), an Argentinian molecular biologist, and Georges Köhler, a German immunologist, perfected the technique of monoclonal antibody production from hybridomas, for which they shared the Nobel Prize in Medicine. This discovery proved the validity of the clonal selection theory of antibody formation. On receiving the PhD in Biochemistry in Buenos Aries, he completed a second doctorate at Cambridge. On joining the staff of the Medical Research Council of Molecular Biology, Milstein et al. established the complete sequence of an immunoglobulin light chain. They discovered only one type of messenger ribonucleic acid (RNA) for both constant and variable light chain domains. Milstein reasoned that the constant domain genes must come together in antibody‐synthesising cells. Milstein and Köhler fused antibody‐forming spleen cells with mutant myeloma cells to form hybridomas to study the genetic basis of antibody diversity. The mutant myeloma cells conferred immortality on the fused cell line, whereas the spleen cells conferred antibody specificity. Thus, the hybrid cell or hybridoma cell line exhibited long‐term survival in culture, producing an unlimited quantity of monoclonal antibodies.

Keywords: hybridoma; monoclonal antibodies; clonal selection; mutant myeloma cells; antibody‐synthesising cells

Figure 1.

César Milstein. Photograph from the private collection of Julius M. Cruse, MD, PhD. © Julius M. Cruse.


Further Reading

Clark WR (1991) The Experimental Foundations of Modern Immunology. New York: John Wiley.

Goding JW (1986) Monoclonal Antibodies: Principles and Practice. Production and Application of Monoclonal Antibodies in Cell Biology, Biochemistry and Immunology, 2nd edn. London: Academic Press.

Hurrell JGR (eds) (1982) Monoclonal Hybridoma Antibodies: Techniques and Applications. Boca Raton: CRC Press.

Köhler GF and Milstein C (1975) Continuous cultures of fused cells secreting antibody of predefined specificity. Nature 256: 495–497.

LeBlanc PA (1985) Monoclonal antibodies: novel to Nobel. In: Cruse JM and Lewis RE (eds) The Year in Immunology 1984–85, pp. 136–142. Basel: Karger.

McMichael AJ and Fabre JW (eds) (1982) Monoclonal Antibodies in Clinical Medicine. London: Academic Press.

Milstein C (1982) Monoclonal antibodies from hybrid myelomas: theoretical aspects and some general comments. In: McMichael AJ and Febre JW (eds) Monoclonal Antibodies in Clinical Medicine, pp. 3–13. London: Academic Press.

Milstein C (1986) From antibody structure to immunological diversification of immune response. Science 231: 1261–1268.

Wade N (1982) Hybridomas: the making of a revolution. Science 215: 1073–1075.

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How to Cite close
Cruse, Julius M, and Lewis, Robert E(May 2014) Milstein, César. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0002877.pub2]