Genetic timestamping of plasma cells in vivo reveals homeostatic population turnover

Abstract

AbstractPlasma cells (PC)s are essential for protection from infection, and at the origin of incurable cancers. Current studies do not circumvent limitations of removing PCs from their microenvironment and confound formation and maintenance. This is in part due to the lack of tools to perform specific genetic manipulation in vivo. Also, studies of PC population dynamics have mostly relied on the use of nucleotide analog incorporation that does not label quiescent cells, a property of most PCs. Here we characterize in detail a genetic tool (JchaincreERT2) that permits first-ever specific genetic manipulation in PC in vivo, across immunoglobulin isotypes. Using this tool we found that PC numbers remained constant over-time and that PC decay was compensated by the emergence of new cells, supporting an homeostatic turnover of the population. The JchaincreERT2 genetic tool paves the way for in-depth mechanistic understanding of PC biology and pathology in vivo, in their microenvironment.HighlightsJchain expression occurs in most plasma cells across immunoglobulin isotypesJchaincreERT2 mediated genetic manipulation is effective only in plasma cellsGenetic timestamping of plasma cells reveals homeostatic regulation