B cell activation involves nanoscale receptor reorganizations and inside-out signaling by Syk

Elife. 2014 Jun 24:3:e02069. doi: 10.7554/eLife.02069.

Abstract

Binding of antigen to the B cell antigen receptor (BCR) initiates a multitude of events resulting in B cell activation. How the BCR becomes signaling-competent upon antigen binding is still a matter of controversy. Using a high-resolution proximity ligation assay (PLA) to monitor the conformation of the BCR and its interactions with co-receptors at a 10-20 nm resolution, we provide direct evidence for the opening of BCR dimers during B cell activation. We also show that upon binding Syk opens the receptor by an inside-out signaling mechanism that amplifies BCR signaling. Furthermore, we found that on resting B cells, the coreceptor CD19 is in close proximity with the IgD-BCR and on activated B cells with the IgM-BCR, indicating nanoscale reorganization of receptor clusters during B cell activation.DOI: http://dx.doi.org/10.7554/eLife.02069.001.

Keywords: B cell antigen receptor; inside-out signaling; nanoscale receptor organization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / metabolism*
  • Cell Line
  • Dimerization
  • Humans
  • Lymphocyte Activation*
  • Mice
  • Receptors, Antigen, B-Cell / metabolism*
  • Signal Transduction*

Substances

  • Receptors, Antigen, B-Cell

Grants and funding

The funder had no role in study design, data collection and interpretation, or the decision to submit the work for publication.