IgA:IgM and IgA:IgA hybrid hybridomas secrete heteropolymeric immunoglobulins that are polyvalent and bispecific

H. B. Urnovitz, Y. Chang, M. Scott, J. Fleischman, R. G. Lynch

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Polyvalent bispecific antibodies were secreted by hybridoma cells when both parental clones expressed a naturally polymerizing immunoglobulin. Hybrid hybridomas made from IgA λ2 anti-trinitrophenyl (TNP) and IgA κ anti-phosphocholine (PC) parental cells secreted polymeric IgA antibodies that bound both TNP and PC. Some of the TNP binding was dissociated from the PC binding under conditions of mild reduction and alkylation suggesting that the bispecific polymeric IgA contained disulfide-linked parental monomers as well as bispecific hybrid monomers. Hybrid hybridomas constructed from IgA λ2 anti-TNP and IgM κ anti-ox erythrocyte parental cells secreted bispecific, polymeric immunoglobulin that contained μ-, α-, κ-, and λ2-chains. The μ and κ-chains dissociated from the α- and λ2-chains under conditions of mild reduction and alkylation, indicating that both parental monomers had been incorporated into the same polymeric immunoglobulin to form a heteropolymeric antibody molecule. Heterologous pairing of α and μ heavy chains in monomers was not detected. Hybrid hybridomas constructed from IgA λ2 and IgG3 λ2 or IgA λ2 and IgG1 κ parents co-secreted both parental immunoglobulins, but the antibodies secreted by these clones did not form heteropolymers or exhibit heterologous heavy chain pairing. These findings establish that polyvalent, bispecific, polymeric immunoglobulin molecules can be produced by hybrid hybridomas when both parents express a naturally polymerizing class of heavy chain but not when only one parent does. Hybrid hybridomas that produce heteropolymeric immunoglobulins are sources of high avidity bispecific antibodies that may find a number of basic and practical applications. The hybridoma cells that produce these antibodies may provide useful tools for investigating the in situ determinants of immunoglobulin chain association and the regulation of antibody assembly and secretion.

Original languageEnglish (US)
Pages (from-to)558-563
Number of pages6
JournalJournal of Immunology
Volume140
Issue number2
StatePublished - Jan 1 1988
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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