| Literature DB >> 26140596 |
Taia T Wang1, Jad Maamary1, Gene S Tan2, Stylianos Bournazos1, Carl W Davis3, Florian Krammer2, Sarah J Schlesinger4, Peter Palese5, Rafi Ahmed3, Jeffrey V Ravetch6.
Abstract
Protective vaccines elicit high-affinity, neutralizing antibodies by selection of somatically hypermutated B cell antigen receptors (BCR) on immune complexes (ICs). This implicates Fc-Fc receptor (FcR) interactions in affinity maturation, which, in turn, are determined by IgG subclass and Fc glycan composition within ICs. Trivalent influenza virus vaccination elicited regulation of anti-hemagglutinin (HA) IgG subclass and Fc glycans, with abundance of sialylated Fc glycans (sFc) predicting quality of vaccine response. We show that sFcs drive BCR affinity selection by binding the Type-II FcR CD23, thus upregulating the inhibitory FcγRIIB on activated B cells. This elevates the threshold requirement for BCR signaling, resulting in B cell selection for higher affinity BCR. Immunization with sFc HA ICs elicited protective, high-affinity IgGs against the conserved stalk of the HA. These results reveal a novel, endogenous pathway for affinity maturation that can be exploited for eliciting high-affinity, broadly neutralizing antibodies through immunization with sialylated immune complexes.Entities:
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Year: 2015 PMID： 26140596 PMCID： PMC4594835 DOI： 10.1016/j.cell.2015.06.026
Source DB: PubMed Journal: Cell ISSN： 0092-8674 Impact factor: 41.582