Unbiased Identification of Novel Plasma Cell Markers Across Mouse and Man

Abstract Naïve B cells differentiate into short-term and long-lived plasma cells (PCs) following pathogen exposure, contributing to the overall humoral immune response. However, an extensive comparison of murine and human antibody secreting cells (ASCs) that integrates surface phenotype and intracellular function is lacking. Mapping B cell lineage populations across diverse tissues in mouse and man is important for vaccine efficacy and clinical immuno-monitoring. In this study, we interrogated relatively unattainable tissues from normal donors such as BM, LN, and gut through LEGENDScreen and exploited an unbiased algorithmic pipeline to visualize broader population structure. We found similarities across species with potential novelty in PC surface markers including CD134/OX40, CD172/Sirpa, CD180/RP105, CD28, CD88/C5aR, CD79b/IgBeta, CD162/PSGL1, CD74/CLIP, CD7, CD360/IL-21R, and CD220/Insr. Expression of these markers are being validated through conventional flow cytometry and scRNA-sequencing, and we are assessing functionality of novel PC subsets in vivo and in vitro. Exposing the distribution of PC subsets and functional diversity in different tissue sites across human and murine models will help validate survival pathways, and provide new insights on the subsets that support long-lived humoral immune responses throughout the body.