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.
Highlights
It is clear that neutralization of toxins by Ab plays a major role in protective immunity
Both Fab and F(ab’)2 fragments were made from RAC18, a murine IgG2a/κ, F(ab’)2 fragments were only used in Enzyme Linked ImmunoSorbent Assay (ELISA)
We study the role of the Fc region of neutralizing Abs in protection from the toxic effects of ricin administration
Summary
It is clear that neutralization of toxins by Ab plays a major role in protective immunity. We generally teach our students that Ab functions by preventing attachment and internalization of the toxin to target cells [1,2], suggesting that anti-B chain immunity would be paramount. Knockout mice, suggests that FcR function is a “requirement” for protection against anthrax toxin [9,10]. In this manuscript, we further examine this apparent paradox, employing ricin-neutralizing Abs to study the role of Fc-mediated protection. We further examine this apparent paradox, employing ricin-neutralizing Abs to study the role of Fc-mediated protection Both monoclonal (mAbs) and polyclonal (pAbs) were used to evaluate protection of individual cells and in mice. Abs into the cells by FcRγ have upon intracellular neutralization of ricin toxicity [4]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
