Villar, Rina F.Patel, JinalWeaver, Grant C.Kanekiyo, MasaruWheatley, Adam K.Yassine, Hadi M.Costello, Catherine E.Chandler, Kevin B.McTamney, Patrick. M.Nabel, Gary J.McDermott, Adrian B.Mascola, John R.Carr, Steven A.Lingwood, Daniel2016-12-022016Villar, R. F., J. Patel, G. C. Weaver, M. Kanekiyo, A. K. Wheatley, H. M. Yassine, C. E. Costello, et al. 2016. “Reconstituted B cell receptor signaling reveals carbohydrate-dependent mode of activation.” Scientific Reports 6 (1): 36298. doi:10.1038/srep36298. http://dx.doi.org/10.1038/srep36298.2045-2322http://nrs.harvard.edu/urn-3:HUL.InstRepos:29626094Activation 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.en-USJournal Article2016-12-0210.1038/srep36298