A requirement for FcγR in antibody-mediated bacterial toxin neutralization

Nareen Abboud, Siu Kei Chow, Carolyn Saylor, Alena Janda, Jeffery V. Ravetch, Matthew D. Scharff, Arturo Casadevall

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Abstract

One important function of humoral immunity is toxin neutralization. The current view posits that neutralization results from antibody-mediated interference with the binding of toxins to their targets, a phenomenon viewed as dependent only on antibody specificity. To investigate the role of antibody constant region function in toxin neutralization, we generated IgG2a and IgG2b variants of the Bacillus anthracis protective antigen-binding IgG1 monoclonal antibody (mAb) 19D9. These antibodies express identical variable regions and display the same specificity. The efficacy of antibody-mediated neutralization was IgG2a > IgG2b > IgG1, and neutralization activity required competent Fcγ receptor (FcγR). The IgG2a mAb prevented lethal toxin cell killing and mitogen-activated protein kinase/extracellular signal-regulated kinase kinase cleavage more efficiently than the IgG1 mAb. Passive immunization with IgG1 and IgG2a mAb protected wild-type mice, but not FcγR-deficient mice, against B. anthracis infection. These results establish that constant region isotype influences toxin neutralization efficacy of certain antibodies through a mechanism that requires engagement of FcγR. These findings highlight a new parameter for evaluating vaccine responses and the possibility of harnessing optimal FcγR interactions in the design of passive immunization strategies.

Original languageEnglish (US)
Pages (from-to)2395-2405
Number of pages11
JournalJournal of Experimental Medicine
Volume207
Issue number11
DOIs
Publication statusPublished - Oct 25 2010

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Abboud, N., Chow, S. K., Saylor, C., Janda, A., Ravetch, J. V., Scharff, M. D., & Casadevall, A. (2010). A requirement for FcγR in antibody-mediated bacterial toxin neutralization. Journal of Experimental Medicine, 207(11), 2395-2405. https://doi.org/10.1084/jem.20100995