Modeling the longevity and secretory capacity of engineered human plasma cells

Abstract

Due to their unique longevity and capacity to secrete high levels of protein, plasma cells have the potential to be used as a cell therapy for protein replacement. Through CITE-seq and bulk RNA-seq experiments, I showed ex vivo engineered human plasma cells exhibited transcriptional features akin to natural long-lived plasma cells. These engineered cells exhibited altered protein secretion and long-term in vivo engraftment in a humanized IL-6 mouse model. To further study the protein secretion capacity of our engineered plasma cells, we developed a method to associate protein secretion with cell information in a single-cell basis. We were able to analyze thousands of plasma cells directly linking IgG secretion with transcript profile (SEC-seq) and surface markers. Our work has added to our understanding of ex vivo engineered plasma cells and the technology we developed enables exploration of links between genome and secretory function, laying the foundation for numerous discoveries in immunology, stem cell biology, and beyond.