Kavli Affiliate: Robert Edwards
| Authors: Md. Alamgir Hossain, Kara Anasti, Brian Watts, Kenneth Cronin, Advaiti Pai Kane, R.J. Edwards, David Easterhoff, Jinsong Zhang, Wes Rountree, Yaneth Ortiz, Laurent Verkoczy, Michael Reth and S. Munir Alam
| Summary:
HIV-1 Envelope (Env) proteins designed to induce neutralizing antibody responses allow study of the role of affinities (equilibrium dissociation constant, KD) and kinetic rates (association/dissociation rates) on B cell antigen recognition. It is unclear whether affinity discrimination during B cell activation is based solely on Env protein binding KD, and whether B cells discriminate between proteins of similar affinities but that bind with different kinetic rates. Here we used a panel of Env proteins and Ramos B cell lines expressing IgM BCRs with specificity for CD4 binding-site broadly neutralizing (bnAb) or a precursor antibody to study the role of antigen binding kinetic rates on both early (proximal/distal signaling) and late events (BCR/antigen internalization) in B cell activation. Our results support a kinetic model for B cell activation in which Env protein affinity discrimination is based not on overall KD, but on sensing of association rate and a threshold antigen-BCR half-life.