In this application note, we demonstrate how Opto Plasma B Discovery enables the rapid selection of receptor-ligand blocking antibodies using the therapeutically-relevant PD-1/PD-L1 model system. We also show that by screening not only primary single B cells from the spleen but also those from bone marrow, we were able to discover more blocking antibodies and identify unique candidates that may be missed using traditional hybridoma technology. Using the PD-1/PD-L1 interaction as a model system, we demonstrate that multiple binding and blocking assays enable the selection of 46 unique lead candidates capable of blocking the interaction between PD-1 and PD-L1. We also show that 3x as many antibodies can be identified using bone marrow B cells compared to B cells from the spleen, expanding the diversity of lead candidates. The ability to perform a comprehensive screen on the B cell repertoire using multiple assays to identify functionally-relevant lead candidates against your target of interest – in just one day – may reduce the time and effort to bring new, efficacious therapies to the clinic.