The membrane skeleton controls diffusion dynamics and signaling through the B cell receptor

Immunity. 2010 Feb 26;32(2):187-99. doi: 10.1016/j.immuni.2009.12.005. Epub 2010 Feb 18.

Abstract

Early events of B cell activation after B cell receptor (BCR) triggering have been well characterized. However, little is known about the steady state of the BCR on the cell surface. Here, we simultaneously visualize single BCR particles and components of the membrane skeleton. We show that an ezrin- and actin-defined network influenced steady-state BCR diffusion by creating boundaries that restrict BCR diffusion. We identified the intracellular domain of Igbeta as important in mediating this restriction in diffusion. Importantly, alteration of this network was sufficient to induce robust intracellular signaling and concomitant increase in BCR mobility. Moreover, by using B cells deficient in key signaling molecules, we show that this signaling was most probably initiated by the BCR. Thus, our results suggest the membrane skeleton plays a crucial function in controlling BCR dynamics and thereby signaling, in a way that could be important for understanding tonic signaling necessary for B cell development and survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / immunology
  • Actins / metabolism*
  • Animals
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism*
  • B-Lymphocytes / pathology
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacology
  • CD79 Antigens / genetics
  • CD79 Antigens / immunology
  • CD79 Antigens / metabolism*
  • Cell Line, Tumor
  • Cell Membrane / drug effects
  • Cell Membrane / immunology*
  • Cell Membrane / metabolism
  • Cytoskeletal Proteins / immunology
  • Cytoskeletal Proteins / metabolism*
  • Cytoskeleton / drug effects
  • Cytoskeleton / immunology
  • Immunologic Capping / drug effects
  • Immunologic Capping / genetics
  • Immunologic Capping / immunology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microscopy, Fluorescence
  • Protein Binding
  • Protein Engineering
  • Protein Structure, Tertiary / genetics
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Signal Transduction / immunology
  • Thiazolidines / pharmacology

Substances

  • Actins
  • Bridged Bicyclo Compounds, Heterocyclic
  • CD79 Antigens
  • Cytoskeletal Proteins
  • Thiazolidines
  • ezrin
  • latrunculin A