Reconstituted B cell receptor signaling reveals carbohydrate-dependent mode of activation

Rina F. Villar, Jinal Patel, Grant C. Weaver, Masaru Kanekiyo, Adam K. Wheatley, Hadi M. Yassine, Catherine E. Costello, Kevin B. Chandler, Patrick M. McTamney, Gary J. Nabel, Adrian B. McDermott, John R. Mascola, Steven A. Carr, Daniel Lingwood

Research output: Contribution to journalArticlepeer-review

Abstract

Activation 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.

Original languageEnglish (US)
Article number36298
JournalScientific Reports
Volume6
DOIs
StatePublished - Oct 31 2016
Externally publishedYes

ASJC Scopus subject areas

  • General

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