Antigen-specific antibody Fc glycosylation enhances humoral immunity via the recruitment of complement
Name
eaat7796.full.pdf
Description
Published version
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614.9 KB
Format
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Checksum (MD5)
b98b5a248590a8b9f759126d9e1b90bb
Author(s)
Lofano, Giuseppe
Gorman, Matthew J.
Yousif, Ashraf S.
Yu, Wen-Han
Fox, Julie M.
Dugast, Anne-Sophie
Ackerman, Margaret E.
Suscovich, Todd J.
Weiner, Joshua
Barouch, Dan
Date Issued
August 2018
Journal
Science Immunology
Publisher
American Association for the Advancement of Science (AAAS)
Citation
Lofano, Giuseppe et al. "Antigen-specific antibody Fc glycosylation enhances humoral immunity via the recruitment of complement." Science Immunology 3, 26 (August 2018): eaat7796 © 2018 The Authors
Version
Final published version
Abstract
HIV-specific broadly neutralizing antibodies (bNAbs) confer protection after passive immunization, but the immunological mechanisms that drive their development are poorly understood. Structural features of bNAbs indicate that they originate from extensive germinal center (GC) selection, which relies on persistent GC activity. However, why a fraction of infected individuals are able to successfully drive more effective affinity maturation is unclear. Delivery of antigens in the form of antibody-immune complexes (ICs), which bind to complement receptors (CRs) or Fc receptors (FcRs) on follicular dendritic cells, represents an effective mechanism for antigen delivery to the GC. We sought to define whether IC-FcR or CR interactions differ among individuals who develop bNAb responses to HIV. Enhanced Fc effector functions and FcR/CR interactions, via altered Fc glycosylation profiles, were observed among individuals with neutralizing antibody responses to HIV compared with those without neutralizing antibody activity. Moreover, both polyclonal neutralizer ICs and monoclonal IC mimics of neutralizer antibodies induced higher antibody titers, higher-avidity antibodies, and expanded GC B cell reactions after immunization of mice via accelerated antigen deposition within B cell follicles in a complement-dependent manner. Thus, these data point to a direct role for altered Fc profile/complement interactions in shaping the maturation of the humoral immune response, providing insights into how GC activity may be enhanced to drive affinity maturation in next-generation vaccine approaches.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
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Creative Commons Attribution 4.0 International license
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DOI of Published Version
https://doi.org/10.1126/sciimmunol.aat7796
