Antigen-specific antibody Fc glycosylation enhances humoral immunity via the recruitment of complement - PubMed (original) (raw)

. 2018 Aug 17;3(26):eaat7796.

doi: 10.1126/sciimmunol.aat7796.

Matthew J Gorman 1, Ashraf S Yousif 1 2, Wen-Han Yu 1 3, Julie M Fox 4, Anne-Sophie Dugast 1, Margaret E Ackerman 5, Todd J Suscovich 1, Joshua Weiner 5, Dan Barouch 1 6, Hendrik Streeck 7, Susan Little 8, Davey Smith 8 9, Douglas Richman 8 9, Douglas Lauffenburger 3, Bruce D Walker 1 10 11, Michael S Diamond 4, Galit Alter 12

Affiliations

Free PMC article

Antigen-specific antibody Fc glycosylation enhances humoral immunity via the recruitment of complement

Giuseppe Lofano et al. Sci Immunol. 2018.

Free PMC article

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.

Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).

PubMed Disclaimer

References

    1. Immunology. 1978 Apr;34(4):751-61 -PubMed
    1. Scand J Immunol. 2000 Dec;52(6):563-9 -PubMed
    1. Nat Med. 2001 Aug;7(8):899-905 -PubMed
    1. Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):4144-9 -PubMed
    1. Nature. 2003 Mar 20;422(6929):307-12 -PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources