The work by Yea and team* further extends the infective antibody library platform developed by the Lerner team (see commentary: Assay Drug Dev Technol 2013;11:347): in it, antibody libraries are incorporated into lentiviral vectors allowing linking of antibody genotype and phenotype, with the host cell becoming a de facto reporter for the antibody property. While the earlier work utilized a library enriched for binders through a preselection panning step and utilized a reporter to detect a functional outcome, here the system is pushed to the limit by using a naïve library and direct observational selection.
A 108-member naïve human antibody library incorporated into lentiviral vectors was used to infect TF-1 erythroblast cells contained within methylcellulose agar substrate (Figures A, B, and C). Colonies produced in this manner exhibited a range of morphologies that could be singled out through simple direct observation. The authors studied the cellular background of the colonies with the most unusual morphology and identified three antibody clones whose target was determined through mass spectrometry to be primarily the integrin receptor. The antibodies acted as agonists, activating downstream pathways and were further shown to induce human bone marrow CD34+ stem cells to differentiate into cells of the macrophage lineage to form dendritic cells.