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

AM Avalos, AM Bilate, MD Witte, AK Tai, J He… - Journal of Experimental …, 2014 - rupress.org
AM Avalos, AM Bilate, MD Witte, AK Tai, J He, MP Frushicheva, PD Thill, F Meyer-Wentrup…
Journal of Experimental Medicine, 2014rupress.org
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 …
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.
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