B cell receptor-mediated antigen gathering requires ubiquitin ligase Cbl and adaptors Grb2 and Dok-3 to recruit dynein to the signaling microcluster

Immunity. 2011 Jun 24;34(6):905-18. doi: 10.1016/j.immuni.2011.06.001.


The B cell receptor (BCR) mediates B cell antigen gathering and acquisition for presentation to T cells. Although the amount of antigen presentation to T cells determines the extent of B cell activation, the molecular mechanisms underlying antigen gathering remain unexplored. Here, through a combination of high-resolution imaging, genetics and quantitative mass spectrometry, we demonstrate that adaptors Grb2 and Dok-3, and ubiquitin ligase Cbl in signaling BCR microclusters mediate association with the microtubule motor dynein. Furthermore, we visualize the localization and movement of these microclusters on the underlying microtubule network. Importantly, disruption of this network or diminished dynein recruitment in Grb2-, Dok-3-, or Cbl-deficient B cells, does not influence microcluster formation or actin-dependent spreading, but abrogates directed movement of microclusters and antigen accumulation. Thus we identify a surprising but pivotal role for dynein and the microtubule network alongside Grb2, Dok-3, and Cbl in antigen gathering during B cell activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / immunology*
  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Antigens / immunology*
  • Cells, Cultured
  • Dyneins / immunology*
  • Dyneins / metabolism
  • GRB2 Adaptor Protein / immunology*
  • GRB2 Adaptor Protein / metabolism
  • Mice
  • Microtubules / metabolism
  • Protein Binding
  • Proto-Oncogene Proteins c-cbl / immunology*
  • Proto-Oncogene Proteins c-cbl / metabolism
  • Receptors, Antigen, B-Cell / immunology*
  • Receptors, Antigen, B-Cell / metabolism
  • Signal Transduction*
  • Tubulin / metabolism


  • Adaptor Proteins, Signal Transducing
  • Antigens
  • Dok3 protein, mouse
  • GRB2 Adaptor Protein
  • Grb2 protein, mouse
  • Receptors, Antigen, B-Cell
  • Tubulin
  • Proto-Oncogene Proteins c-cbl
  • Dyneins
  • Cbl protein, mouse