Hybrid hybridomas and their use in immunohistochemistry

Nature. 1983 Oct 6-12;305(5934):537-40. doi: 10.1038/305537a0.


A normal antibody-producing cell only expresses one antibody, resulting in the well-known phenomenon of allelic exclusion. When two myeloma cells are fused, the derived hybrids are capable of co-dominantly expressing the antibody genes of both parents. Although the respective variable (V) and constant (C) region genes remain expressed in the same cis configuration, heavy and light chains of both parents are scrambled, and hybrid molecules are formed. The same is true when a myeloma and an antibody-producing cell are fused to produce a hybrid myeloma (hybridoma). Fusion therefore allows the production of hybrid immunoglobulin molecules containing two different combining sites. Hybrid molecules of this type retain antigen-binding activity and specificity. Bispecific monoclonal antibodies secreted by hybridomas may have a variety of uses in biology and in medicine. Here we have focused on their application in histochemistry. As an example, we have prepared and tested an anti-somatostatin-anti-peroxidase bispecific antibody. This way of producing hybrid molecules is superior to the production of hybrid antibodies by chemical reconstitution methods because the drastic treatment required for chain separation in the latter is likely to lead to some protein denaturation and loss of antibody activity. Intracellularly synthesized and assembled hybrids do not suffer from this disadvantage. In addition, the recombination of heavy and light chains from different antibody molecules is likely to lead to considerable waste.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibody Specificity
  • Hybrid Cells / immunology
  • Hybridomas / immunology*
  • Immunoenzyme Techniques
  • Immunoglobulin G / immunology
  • Immunoglobulin M / immunology
  • Immunologic Techniques
  • Mice
  • Peroxidases / immunology
  • Somatostatin / immunology


  • Immunoglobulin G
  • Immunoglobulin M
  • Somatostatin
  • Peroxidases