Mapping the formation of protective antibody responses

Biological responses typically follow distributions that can be modelled mathematically, conforming to standard structures. In recent work, we assessed the death rate of antibody-producing cells (PC), and found that the underlying structure is likely a survival maximum for each cell drawn from a continuum, with cells falling into continua of short-lived and long-lived states. The long-lived state is of interest, as these are the cells that protect individuals from infections (viruses, bacteria, fungi, parasites) for many years, and also cause years-long allergies (to peanuts, tree nuts, dust mites and environmental toxins). Here, we seek to establish through a series of experiments, how that population structure is laid down. We will use a novel bone marrow transplant model to assess carriage capacity of femurs, and PC fate-mapping, a genetic tool that means extant PC are traced in time, to reveal the decay structure. We will use competitive and non-competitive scenarios to look at what features make PC long-lived and able to protect for long timespans versus predict a short-lived trajectory. Mouse models, high dimension flow cytometry, including spectral flow, surgery techniques, mouse handling, mathematic modelling, RNAseq, scRNAseq and ATACseq will be applied in the work.