Intrinsic Properties of Immunoglobulin IgG1 Isotype-Switched B Cell Receptors Promote Microclustering and the Initiation of Signaling

Immunity. 2010 Jun 25;32(6):778-89. doi: 10.1016/j.immuni.2010.06.006.

Abstract

Memory B cells express high-affinity, immunoglobulin GB cell receptors (IgG BCRs) that enhance B cell responses, giving rise to the rapid production of high-affinity, IgG antibodies. Despite the central role of IgG BCRs in memory responses, the mechanisms by which the IgG BCRs function to enhance B cell responses are not fully understood. Using high-resolution live-cell imaging, we showed that IgG1 BCRs dramatically enhanced the earliest BCR-intrinsic events that followed within seconds of B cells' encounter with membrane bound antigen, including BCR oligomerization and BCR microcluster growth, leading to Syk kinase recruitment and calcium responses. The enhancement of these early events was dependent on a membrane proximal region of the IgG1 cytoplasmic tail not previously appreciated to play a role in IgG1 BCR signaling. Thus, intrinsic properties of the IgG1 BCR enhance early antigen-driven events that ultimately translate into heightened signaling.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Calcium / immunology
  • Calcium / metabolism
  • Cell Membrane / immunology
  • Cell Membrane / metabolism
  • Immunoglobulin Class Switching / immunology*
  • Immunoglobulin G / immunology*
  • Immunoglobulin G / metabolism
  • Intracellular Signaling Peptides and Proteins / immunology
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Lymphocyte Activation / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Protein-Tyrosine Kinases / immunology
  • Protein-Tyrosine Kinases / metabolism
  • Receptors, Antigen, B-Cell / immunology*
  • Receptors, Antigen, B-Cell / metabolism
  • Signal Transduction / immunology*
  • Syk Kinase
  • Transfection

Substances

  • Immunoglobulin G
  • Intracellular Signaling Peptides and Proteins
  • Receptors, Antigen, B-Cell
  • Protein-Tyrosine Kinases
  • Syk Kinase
  • Syk protein, mouse
  • Calcium