A Revolution in Immunology Monoclonal Antibodies

Richard A. Goldsby, professor, Department of Biology, Amherst College, Amherst, MA.

The construction of antibody-secreting cell lines hybridomas--by fusing antibody-secreting lymphocytes with appropriate tumor cell lines myelomas has forever changed immunology. Indeed, the monoclonal revolution has spread far beyond the shores of its mother discipline and now laps the coasts of biochemistry, neurobiology, developmental biology, agriculture, medicine and toxicology.

This article will describe the technology of hybridoma production. A companion piece by David Snyder tells how monoclonal antibodies are used to solve many problems.

Hybridoma technology, like recombinant DNA technology, is rooted in basic biology and is the capstone of years of basic research in cell fusion. It is a procedure in which two different kinds of cells are artificially caused to fuse to forma single hybrid cell. Such hybrids are particularly interesting because they incorporate the genetic potential of both parent cells. This technique has made it possible to construct and study the properties of cell hybrids made from such combinations as normal cells with cancer cells, mouse cells with human cells, and even human cells with those of mosquitoes.

Plant virologist checks the temperature of liquid nitrogen storage tanks in which hybridomas are preserved.

Early Research

In 1973, Jerold Schwaber and Ed Cohen, working at the University of Chicago's LaRibida Institute, were the first to produce antibody-secreting hybridomas by fusing normal antibody-producing human cells (B lymphocytes or B cells) to antibody-producing mouse tumor (myeloma) cells. Their hybridomas displayed the capacity for unlimited growth in culture characteristic of the myeloma parent while retaining the antibody-producing characteristics of the normal B cell.

But it was George Kohler and Cesar Milstein who devised and demonstrated a deliberate and rational strategy for the construction of continuous cell lines which secrete monoclonal antibodies of a desired specificity. In 1975 they fused a mouse myeloma cell line with lymphocytes from mice that had been previously immunized with a particular antigen. They then screened the resulting hybridoma clones to identify those that were secreting monoclonal antibodies specific for the immunizing antigen. Their success, which has been widely reproduced, revolutionized immunology and created an industry.