Avalos, Ana M.Bilate, Angelina M.Witte, Martin D.Tai, Albert K.He, JiangFrushicheva, Maria P.Thill, Peter D.Meyer-Wentrup, FriederikeTheile, Christopher S.Chakraborty, Arup K.Zhuang, XiaoweiPloegh, Hidde L.2014-09-082014Avalos, A. M., A. M. Bilate, M. D. Witte, A. K. Tai, J. He, M. P. Frushicheva, P. D. Thill, et al. 2014. “Monovalent engagement of the BCR activates ovalbumin-specific transnuclear B cells.” The Journal of Experimental Medicine 211 (2): 365-379. doi:10.1084/jem.20131603. http://dx.doi.org/10.1084/jem.20131603.0022-1007http://nrs.harvard.edu/urn-3:HUL.InstRepos:12785859Valency 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.en-USJournal Article2014-09-0810.1084/jem.20131603