Monovalent engagement of the BCR activates ovalbumin-specific transnuclear B cells
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.; Zhuang, Xiaowei; Ploegh, Hidde; ... Show more Show less
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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.
DepartmentInstitute for Medical Engineering and 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
Journal of Experimental Medicine
Rockefeller University Press
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.
Final published version