Role of Fc in antibody-mediated protection from ricin toxin

Seth H. Pincus, Anushka Das, Kejing Song, Grace A. Maresh, Miriam Corti, Jody Berry

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

We have studied the role of the antibody (Ab) Fc region in mediating protection from ricin toxicity. We compared the in vitro and in vivo effects of intact Ig and of Fab fragments derived from two different neutralizing Ab preparations, one monoclonal, the other polyclonal. Consistent results were obtained from each, showing little difference between Ig and Fab in terms of antigen binding and in vitro neutralization, but with relatively large differences in protection of animals. We also studied whether importing Ab into the cell by Fc receptors enhanced the intracellular neutralization of ricin toxin. We found that the imported Ab was found in the ER and Golgi, a compartment traversed by ricin, as it traffics through the cell, but intracellular Ab did not contribute to the neutralization of ricin. These results indicate that the Fc region of antibody is important for in vivo protection, although the mechanism of enhanced protection by intact Ig does not appear to operate at the single cell level. When using xenogeneic antibodies, the diminished immunogenicity of Fab/F(ab')2 preparations should be balanced against possible loss of protective efficacy.

Original languageEnglish (US)
Pages (from-to)1512-1525
Number of pages14
JournalToxins
Volume6
Issue number5
DOIs
StatePublished - May 7 2014
Externally publishedYes

Keywords

  • Fab
  • Fc receptor
  • Fc region
  • In vivo protection
  • Monoclonal antibody
  • Neutralization
  • Polyclonal antiserum
  • Ricin

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

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