How do infection and inflammation change plasma cell lifespan?

Plasma cells (PC) are the only cell type secreting antibodies, which are important for protective immunity to fight against pathogens. However, factors contributing to PC lifespan are still under investigation. Our work together with studies from other groups suggest that different immune responses may program different lifespan of PC. In addition, extrinsic factors may also affect the turnover of existing PC. The goal of this project is to understand PC lifespan regulation, particularly to understand how infection and inflammation may change plasma cell lifespan. It will use the BLTcre.Mcl1f/+ PC-timestamping mice to track PC turnover in time. Our specific aims and brief experimental plans are: 1. Quantify turnover of PC generated by different immunisations. BLTcre.Mcl1f/+ mice will be infected by PR8 influenza virus intranasally or immunised with PR8 HA protein in alhydrogel intramuscularly. We will quantify HA-specific PC turnover in lymph node, spleen and bone marrow over time. If we identify conditions associated with different PC lifespans, we will perform RNA-sequencing of the PC to reveal molecular features that distinguish lifespan potentials of PC. 2. Determine the effect on the turnover of existing PC by infection and inflammation We will timestamp the BLTcre.Mcl1f/+ mice and then give the mice 1) PR8 influenza virus infection, 2) TNF-a (a pro-inflammatory cytokine) or 3) IL-6 (a pro-inflammatory cytokine). We will trace the numbers and percentages of timestamped PC over a time course to reveal the effect of each of these factors on PC survival. The main techniques that will be involved in this project are: 1) Multicolor flow cytometry 2) Cell culture 3) RNA sequencing 4) Basic bioinformatics 5) Animal model handling (if needed) The student will not only learn the techniques mentioned above, but also have the opportunity to participate in the cutting-edge research in a supportive working environment. We don't just do experiments. We explore, discuss, and we try to develop our own way of scientific thinking altogether. This project will be conducted in Prof. David Tarlinton's lab at Department of Immunology based at the Alfred Research Alliance precinct.