B-cell tolerance to the B-cell receptor variable regions

Eur J Immunol. 2013 Oct;43(10):2577-87. doi: 10.1002/eji.201243203. Epub 2013 Jul 19.

Abstract

An enormous number of B cells with different B-cell receptors (BCRs) are continuously produced in the bone marrow. BCRs are further diversified during the germinal center reaction. Due to extensive recirculation, B cells with mutually binding BCR are likely to meet in lymphoid organs. We have addressed possible outcomes of such an encounter in vitro. B lymphoma cells were transfected with complementary BCR, one transfectant expressing an Idiotype⁺ (Id⁺) BCR and the other an anti-Id BCR. To exclude confounding effects of secreted Ig, the transfected B lymphoma cells only expressed membrane IgD. Coincubation of paired Id⁺/anti-Id lymphoma cells results in conjugate formation, signaling, activation of Caspase 3/7, and apoptosis of at least one of the two cells in the pair. Our data provide suggestive evidence for a mechanism whereby the B-cell compartment is partly purged of B cells with complementary BCRs.

Keywords: Apoptosis; B-cell receptor (BCR); Idiotypes; Tolerance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Anti-Idiotypic / genetics
  • Antibodies, Anti-Idiotypic / metabolism
  • Apoptosis / genetics
  • Apoptosis / immunology
  • B-Lymphocytes / immunology*
  • Bone Marrow / immunology
  • Caspase 3 / metabolism
  • Caspase 7 / metabolism
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • Cell Line, Tumor
  • Coculture Techniques
  • Immune Tolerance*
  • Immunoglobulin D / genetics
  • Immunoglobulin D / metabolism*
  • Immunoglobulin Variable Region / immunology*
  • Lymphocyte Activation / genetics
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Receptors, Antigen, B-Cell / immunology*
  • Signal Transduction / immunology
  • Transgenes / genetics

Substances

  • Antibodies, Anti-Idiotypic
  • Immunoglobulin D
  • Immunoglobulin Variable Region
  • Membrane Proteins
  • Receptors, Antigen, B-Cell
  • Caspase 3
  • Caspase 7