Monovalent engagement of the BCR activates ovalbumin-specific transnuclear B cells

J Exp Med. 2014 Feb 10;211(2):365-79. doi: 10.1084/jem.20131603. Epub 2014 Feb 3.

Abstract

Valency requirements for B cell activation upon antigen encounter are poorly understood. OB1 transnuclear B cells express an IgG1 B cell receptor (BCR) specific for ovalbumin (OVA), the epitope of which can be mimicked using short synthetic peptides to allow antigen-specific engagement of the BCR. By altering length and valency of epitope-bearing synthetic peptides, we examined the properties of ligands required for optimal OB1 B cell activation. Monovalent engagement of the BCR with an epitope-bearing 17-mer synthetic peptide readily activated OB1 B cells. Dimers of the minimal peptide epitope oriented in an N to N configuration were more stimulatory than their C to C counterparts. Although shorter length correlated with less activation, a monomeric 8-mer peptide epitope behaved as a weak agonist that blocked responses to cell-bound peptide antigen, a blockade which could not be reversed by CD40 ligation. The 8-mer not only delivered a suboptimal signal, which blocked subsequent responses to OVA, anti-IgG, and anti-kappa, but also competed for binding with OVA. Our results show that fine-tuning of BCR-ligand recognition can lead to B cell nonresponsiveness, activation, or inhibition.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • Cell Nucleus / immunology
  • Cell Nucleus / metabolism
  • Epitopes / chemistry
  • Epitopes / metabolism
  • Immune Tolerance
  • Ligands
  • Lymphocyte Activation
  • Mice
  • Mice, 129 Strain
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Models, Immunological
  • Ovalbumin / immunology*
  • Ovalbumin / metabolism
  • Protein Multimerization / immunology
  • Receptors, Antigen, B-Cell / metabolism*

Substances

  • Epitopes
  • Ligands
  • Receptors, Antigen, B-Cell
  • Ovalbumin