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AuthorVillar, Rina F.
AuthorPatel, Jinal
AuthorWeaver, Grant C.
AuthorKanekiyo, Masaru
AuthorWheatley, Adam K.
AuthorYassine, Hadi M.
AuthorCostello, Catherine E.
AuthorChandler, Kevin B.
AuthorMcTamney, Patrick M.
AuthorNabel, Gary J.
AuthorMcDermott, Adrian B.
AuthorMascola, John R.
AuthorCarr, Steven A.
AuthorLingwood, Daniel
Available date2016-11-06T06:29:32Z
Publication Date2016-10-31
Publication NameScientific Reports
Identifierhttp://dx.doi.org/10.1038/srep36298
CitationVillar, R. F. et al. Reconstituted B cell receptor signaling reveals carbohydrate dependent mode of activation. Sci. Rep. 6, 36298
URIhttp://hdl.handle.net/10576/4968
AbstractActivation of immune cells (but not B cells) with lectins is widely known. We used the structurally defined interaction between influenza hemagglutinin (HA) and its cell surface receptor sialic acid (SA) to identify a B cell receptor (BCR) activation modality that proceeded through non-cognate interactions with antigen. Using a new approach to reconstitute antigen-receptor interactions in a human reporter B cell line, we found that sequence-defined BCRs from the human germline repertoire could be triggered by both complementarity to influenza HA and a separate mode of signaling that relied on multivalent ligation of BCR sialyl-oligosaccharide. The latter suggested a new mechanism for priming naïve B cell responses and manifested as the induction of SA-dependent pan-activation by peripheral blood B cells. BCR crosslinking in the absence of complementarity is a superantigen effect induced by some microbial products to subvert production of antigen-specific immune responses. B cell superantigen activity through affinity for BCR carbohydrate is discussed.
SponsorHarvard University CFAR grant (P30 AI060354); the William F. Milton Fund; the Gilead Sciences Research Scholars Program in HIV; and an Broad-Ragon ENDHIV Catalytic Grant (jointly awarded to D.L. and S.A.C.). C.E.C and K.B.C. were supported by P41 GM104602 and S10 OD010724 grants.
Languageen
PublisherNature Publishing Group
SubjectGlycobiology
Adaptive immunity
TitleReconstituted B cell receptor signaling reveals carbohydrate-dependent mode of activation
TypeArticle
Volume Number6
ESSN2045-2322


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