Fc Glycan-Mediated Regulation of Placental Antibody Transfer

Publication date: Available online 13 June 2019Source: CellAuthor(s): Madeleine F. Jennewein, Ilona Goldfarb, Sepideh Dolatshahi, Cormac Cosgrove, Francesca J. Noelette, Marina Krykbaeva, Jishnu Das, Aniruddh Sarkar, Matthew J. Gorman, Stephanie Fischinger, Carolyn M. Boudreau, Joelle Brown, Jennifer H. Cooperrider, Jasneet Aneja, Todd J. Suscovich, Barney S. Graham, Georg M. Lauer, Tessa Goetghebuer, Arnaud Marchant, Douglas LauffenburgerSummaryDespite the worldwide success of vaccination, newborns remain vulnerable to infections. While neonatal vaccination has been hampered by maternal antibody-mediated dampening of immune responses, enhanced regulatory and tolerogenic mechanisms, and immune system immaturity, maternal pre-natal immunization aims to boost neonatal immunity via antibody transfer to the fetus. However, emerging data suggest that antibodies are not transferred equally across the placenta. To understand this, we used systems serology to define Fc features associated with antibody transfer. The Fc-profile of neonatal and maternal antibodies differed, skewed toward natural killer (NK) cell-activating antibodies. This selective transfer was linked to digalactosylated Fc-glycans that selectively bind FcRn and FCGR3A, resulting in transfer of antibodies able to efficiently leverage innate immune cells present at birth. Given emerging data that vaccination may direct antibody glycosylation, our study provides insights for the development of next-generation mater...
Source: Cell - Category: Cytology Source Type: research

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