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Arp2/3 complex-driven spatial patterning of the BCR enhances immune synapse formation, BCR signaling and B cell activation.
Bolger-Munro, Madison; Choi, Kate; Scurll, Joshua M; Abraham, Libin; Chappell, Rhys S; Sheen, Duke; Dang-Lawson, May; Wu, Xufeng; Priatel, John J; Coombs, Daniel; Hammer, John A; Gold, Michael R.
Afiliación
  • Bolger-Munro M; Department of Microbiology and Immunology, University of British Columbia, Vancouver, Canada.
  • Choi K; Life Sciences Institute, I3 Research Group, University of British Columbia, Vancouver, Canada.
  • Scurll JM; Department of Microbiology and Immunology, University of British Columbia, Vancouver, Canada.
  • Abraham L; Life Sciences Institute, I3 Research Group, University of British Columbia, Vancouver, Canada.
  • Chappell RS; Department of Mathematics, Institute of Applied Mathematics, University of British Columbia, Vancouver, Canada.
  • Sheen D; Department of Microbiology and Immunology, University of British Columbia, Vancouver, Canada.
  • Dang-Lawson M; Life Sciences Institute, I3 Research Group, University of British Columbia, Vancouver, Canada.
  • Wu X; Department of Mathematics, Institute of Applied Mathematics, University of British Columbia, Vancouver, Canada.
  • Priatel JJ; Department of Mathematics, Institute of Applied Mathematics, University of British Columbia, Vancouver, Canada.
  • Coombs D; Department of Microbiology and Immunology, University of British Columbia, Vancouver, Canada.
  • Hammer JA; Life Sciences Institute, I3 Research Group, University of British Columbia, Vancouver, Canada.
  • Gold MR; Department of Microbiology and Immunology, University of British Columbia, Vancouver, Canada.
Elife ; 82019 06 03.
Article en En | MEDLINE | ID: mdl-31157616
When B cells encounter antigens on the surface of an antigen-presenting cell (APC), B cell receptors (BCRs) are gathered into microclusters that recruit signaling enzymes. These microclusters then move centripetally and coalesce into the central supramolecular activation cluster of an immune synapse. The mechanisms controlling BCR organization during immune synapse formation, and how this impacts BCR signaling, are not fully understood. We show that this coalescence of BCR microclusters depends on the actin-related protein 2/3 (Arp2/3) complex, which nucleates branched actin networks. Moreover, in murine B cells, this dynamic spatial reorganization of BCR microclusters amplifies proximal BCR signaling reactions and enhances the ability of membrane-associated antigens to induce transcriptional responses and proliferation. Our finding that Arp2/3 complex activity is important for B cell responses to spatially restricted membrane-bound antigens, but not for soluble antigens, highlights a critical role for Arp2/3 complex-dependent actin remodeling in B cell responses to APC-bound antigens.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfocitos B / Activación de Linfocitos / Receptores de Antígenos de Linfocitos B / Transducción de Señal / Proteína 3 Relacionada con la Actina / Sinapsis Inmunológicas / Proteínas Similares a la Angiopoyetina Límite: Animals Idioma: En Revista: Elife Año: 2019 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Linfocitos B / Activación de Linfocitos / Receptores de Antígenos de Linfocitos B / Transducción de Señal / Proteína 3 Relacionada con la Actina / Sinapsis Inmunológicas / Proteínas Similares a la Angiopoyetina Límite: Animals Idioma: En Revista: Elife Año: 2019 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Reino Unido