title: Role of Fc in antibody-mediated protection from ricin toxin.
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.
authors.affiliation: Children's Hospital New Orleans, New Orleans, LA 70118, USA. spincus@chnola-research.org.
authors.forename: Seth H
authors.initials: SH
authors.lastname: Pincus
authors.affiliation: Children's Hospital New Orleans, New Orleans, LA 70118, USA. anushkadas.11@gmail.com.
authors.forename: Anushka
authors.initials: A
authors.lastname: Das
authors.affiliation: Children's Hospital New Orleans, New Orleans, LA 70118, USA. ksong2@lsuhsc.edu.
authors.forename: Kejing
authors.initials: K
authors.lastname: Song
authors.affiliation: Children's Hospital New Orleans, New Orleans, LA 70118, USA. gmaresh10@gmail.com.
authors.forename: Grace A
authors.initials: GA
authors.lastname: Maresh
authors.affiliation: Children's Hospital New Orleans, New Orleans, LA 70118, USA. miriam.corti@cox.net.
authors.forename: Miriam
authors.initials: M
authors.lastname: Corti
authors.affiliation: Cangene Corporation (now Emergent Biosolutions Inc), Winnipeg, MB R3T 5Y3, Canada. jody_berry@bd.com.
authors.forename: Jody
authors.initials: J
authors.lastname: Berry
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology*; D000915:Antibody Affinity; D004721:Endoplasmic Reticulum / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006056:Golgi Apparatus / Q000276:immunology; D007141:Immunoglobulin Fc Fragments / Q000276:immunology*; D051379:Mice; D012276:Ricin / Q000633:toxicity*
chemical_list: D057134:Antibodies, Neutralizing; D007141:Immunoglobulin Fc Fragments; D012276:Ricin