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Antigen footprint governs activation of the B cell receptor.
Ferapontov, Alexey; Omer, Marjan; Baudrexel, Isabelle; Nielsen, Jesper Sejrup; Dupont, Daniel Miotto; Juul-Madsen, Kristian; Steen, Philipp; Eklund, Alexandra S; Thiel, Steffen; Vorup-Jensen, Thomas; Jungmann, Ralf; Kjems, Jørgen; Degn, Søren Egedal.
Afiliación
  • Ferapontov A; Department of Biomedicine, Aarhus University, Aarhus C, Denmark.
  • Omer M; Center for Cellular Signal Patterns (CellPAT), Aarhus University, Aarhus C, Denmark.
  • Baudrexel I; Center for Cellular Signal Patterns (CellPAT), Aarhus University, Aarhus C, Denmark.
  • Nielsen JS; Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Aarhus C, Denmark.
  • Dupont DM; Center for Cellular Signal Patterns (CellPAT), Aarhus University, Aarhus C, Denmark.
  • Juul-Madsen K; Max Planck Institute of Biochemistry, Martinsried, Germany.
  • Steen P; Center for Cellular Signal Patterns (CellPAT), Aarhus University, Aarhus C, Denmark.
  • Eklund AS; Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Aarhus C, Denmark.
  • Thiel S; Center for Cellular Signal Patterns (CellPAT), Aarhus University, Aarhus C, Denmark.
  • Vorup-Jensen T; Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Aarhus C, Denmark.
  • Jungmann R; Department of Biomedicine, Aarhus University, Aarhus C, Denmark.
  • Kjems J; Max Planck Institute of Biochemistry, Martinsried, Germany.
  • Degn SE; Faculty of Physics and Center for Nanoscience, Ludwig Maximilian University, Munich, Munich, Germany.
Nat Commun ; 14(1): 976, 2023 02 22.
Article en En | MEDLINE | ID: mdl-36813795
Antigen binding by B cell receptors (BCR) on cognate B cells elicits a response that eventually leads to production of antibodies. However, it is unclear what the distribution of BCRs is on the naïve B cell and how antigen binding triggers the first step in BCR signaling. Using DNA-PAINT super-resolution microscopy, we find that most BCRs are present as monomers, dimers, or loosely associated clusters on resting B cells, with a nearest-neighbor inter-Fab distance of 20-30 nm. We leverage a Holliday junction nanoscaffold to engineer monodisperse model antigens with precision-controlled affinity and valency, and find that the antigen exerts agonistic effects on the BCR as a function of increasing affinity and avidity. Monovalent macromolecular antigens can activate the BCR at high concentrations, whereas micromolecular antigens cannot, demonstrating that antigen binding does not directly drive activation. Based on this, we propose a BCR activation model determined by the antigen footprint.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Receptores de Antígenos de Linfocitos B / Antígenos Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2023 Tipo del documento: Article País de afiliación: Dinamarca Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Receptores de Antígenos de Linfocitos B / Antígenos Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2023 Tipo del documento: Article País de afiliación: Dinamarca Pais de publicación: Reino Unido