Monovalent engagement of the BCR activates ovalbumin-specific transnuclear B cells
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Avalos-2014-Monovalent engagemen.pdf
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4.2 MB
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Checksum (MD5)
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Author(s)
Avalos, Ana M.
Bilate, Angelina M.
Witte, Martin D.
Tai, Albert K.
He, Jiang
Frushicheva, Maria P.
Thill, Peter Daniel
Meyer-Wentrup, Friederike
Theile, Christopher S.
Chakraborty, Arup K.
Date Issued
February 2014
Journal
Journal of Experimental Medicine
Publisher
Rockefeller University Press
Citation
Avalos, A. M., A. M. Bilate, M. D. Witte, A. K. Tai, J. He, M. P. Frushicheva, P. D. Thill, et al. “Monovalent Engagement of the BCR Activates Ovalbumin-Specific Transnuclear B Cells.” Journal of Experimental Medicine 211, no. 2 (February 3, 2014): 365–379.
Version
Final published version
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.
MIT Department
Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Chemical Engineering
Massachusetts Institute of Technology. Department of Chemistry
Massachusetts Institute of Technology. Department of Physics
Ragon Institute of MGH, MIT and Harvard
Whitehead Institute for Biomedical Research
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DOI of Published Version
https://doi.org/10.1084/jem.20131603
