Chiranjeev Bisht *, Ankit Pandey and Tanay Shukla
Long-lived Plasma Cells (LLPCs), which are largely found in the bone marrow, are necessary for the development of durable antibody protection. However, due to the rarity of LLPC, neither their phenotypes nor their heterogeneity have been able to be identified. We demonstrate that IgG and IgM LLPCs exhibit an EpCAMhiCXCR3- phenotype, whereas IgA LLPCs are Ly6AhiTigit-, using single-cell mRNA sequencing, cytometry, and a genetic pulse-chase mice model. IgA and IgM LLPC compartments contain cells with innate characteristics and public antibodies in contrast to IgG and IgA LLPCs, which are mostly contributed by somatically hyper mutated cells after immunisation or infection. In particular, IgM LLPCs differentiate in a T cell-independent way, are substantially enriched with public clones shared among many individual animals, and have affinity for both self-antigens and microbial-derived antigens. Together, our research demonstrates various paths that LLPCs can take and opens the door to a greater comprehension of the cellular and molecular bases of long-lasting antibody protection.