If we were to track a population over time, one of the most basic and important questions we could ask is: are they evolving?
For example, if we sampled SARS-CoV-2 (the virus that causes COVID-19) in 2020 and in 2022, we would find many new genetic variants that arose in those two years. However, if we sampled a population of elephants from 2020 to 2022, we would likely find little change in their genetics. While both viruses and elephants are evolving, only the viruses are “measurably evolving,” meaning they evolve rapidly enough to detect changes over the sample interval.
This is important because B cells mutate and evolve to produce effective antibodies, but do B cells evolve like viruses, or like elephants? In a paper published in eLife, we developed a method to test for measurable evolution in B cells. Using serially-sampled single cell sequencing data, we then asked whether influenza vaccination stimulates new evolution in B cells. Seasonal flu vaccines often have poor effectiveness, and one hypothesis is that they only re-stimulate old B cell responses without any new evolution. When we looked at B cells in the blood, we found little evolution 60 days following vaccination: elephants all around. But when we looked in the lymph node, where B cell evolution typically occurs, we found plenty of rapid, virus-y evolution. So flu vaccines do stimulate new B cell evolution after all, but it’s only detectable in the lymph nodes. To place these results in context, we surveyed measurable B cell evolution across a large public dataset and found that some conditions, like HIV and early childhood development, had strong evidence of B cell evolution, but most had very little.
Our results make it clear that B cell evolution is highly tissue and condition-dependent. Perhaps vaccines could be designed to better stimulate B cell evolution and, hopefully, protective immunity. Our method is implemented in the R package dowser, and future work in our group will focus not just on detecting evolution, but resolving B cell lineage trees over time.