title: Reconstituted B cell receptor signaling reveals carbohydrate-dependent mode of activation.
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.
authors: The Ragon Institute of Massachusetts General Hospital, The Massachusetts Institute of Technology and Harvard University, 400 Technology Square, Cambridge, MA 02139, USA.
authors: Rina F
authors: RF
authors: Villar
authors: The Broad Institute of The Massachusetts Institute of Technology and Harvard University, 415 Main St, Cambridge, MA 02142, USA.
authors: Jinal
authors: J
authors: Patel
authors: The Ragon Institute of Massachusetts General Hospital, The Massachusetts Institute of Technology and Harvard University, 400 Technology Square, Cambridge, MA 02139, USA.
authors: Grant C
authors: GC
authors: Weaver
authors: Vaccine Research Center, National Institute for Allergy and Infectious Diseases, National Institutes of Health, 40 Convent Drive, Bethesda, MD 20814, USA.
authors: Masaru
authors: M
authors: Kanekiyo
authors: Department of Microbiology and Immunology, University of Melbourne, Peter Doherty Institute for Infection &Immunity, 792 Elizabeth Street, Melbourne, VIC 3000, Australia.
authors: Adam K
authors: AK
authors: Wheatley
authors: Qatar University Biomedical Research Center, P.O. Box 2713-Doha-Qatar, QU-NRC, Qatar.
authors: Hadi M
authors: HM
authors: Yassine
authors: Boston University School of Medicine, 670 Albany Street, Boston MA 02118-2646, USA.
authors: Catherine E
authors: CE
authors: Costello
authors: Boston University School of Medicine, 670 Albany Street, Boston MA 02118-2646, USA.
authors: Kevin B
authors: KB
authors: Chandler
authors: Medimmune, LLC, One MedImmune Way, Gaithersburg, MD 20878, USA.
authors: Patrick M
authors: PM
authors: McTamney
authors: Sanofi, 640 Memorial Drive, Cambridge, MA 02139, USA.
authors: Gary J
authors: GJ
authors: Nabel
authors: Vaccine Research Center, National Institute for Allergy and Infectious Diseases, National Institutes of Health, 40 Convent Drive, Bethesda, MD 20814, USA.
authors: Adrian B
authors: AB
authors: McDermott
authors: Vaccine Research Center, National Institute for Allergy and Infectious Diseases, National Institutes of Health, 40 Convent Drive, Bethesda, MD 20814, USA.
authors: John R
authors: JR
authors: Mascola
authors: The Broad Institute of The Massachusetts Institute of Technology and Harvard University, 415 Main St, Cambridge, MA 02142, USA.
authors: Steven A
authors: SA
authors: Carr
authors: The Ragon Institute of Massachusetts General Hospital, The Massachusetts Institute of Technology and Harvard University, 400 Technology Square, Cambridge, MA 02139, USA.
authors: Daniel
authors: D
authors: Lingwood
mesh_terms: D002241:Carbohydrates / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000276:immunology*; D006801:Humans; D009980:Influenza A virus / Q000235:genetics / Q000276:immunology*; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*
chemical_list: D002241:Carbohydrates; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D011947:Receptors, Antigen, B-Cell; C483468:hemagglutinin, human influenza A virus