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

Ana M. Avalos, Angelina M. Bilate, Martin D. Witte, Albert K. Tai, Jiang He, Maria P. Frushicheva, Peter D. Thill, Friederike Meyer-Wentrup, Christopher S. Theile, Arup K. Chakraborty, Xiaowei Zhuang, Hidde L. Ploegh*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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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.

Original languageEnglish
Pages (from-to)365-379
Number of pages15
JournalJournal of Experimental Medicine
Volume211
Issue number2
DOIs
Publication statusPublished - 10-Feb-2014

Keywords

  • OPTICAL RECONSTRUCTION MICROSCOPY
  • ANTIGEN RECEPTOR
  • T-CELLS
  • EXPRESSION
  • AFFINITY
  • ANTIBODY
  • MICE
  • LYMPHOCYTES
  • INFECTION
  • RESPONSES

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