Phylogenetic analysis of migration, differentiation, and class switching in B cells
The immune system is highly dynamic. Cells migrate between tissues and differentiate into subtypes as part of immune responses. Both processes are critical to B cell biology, but are difficult to study directly in humans. Evolutionary genetics provides a means to fill this gap. For example, B cell lineages sampled in multiple tissues could be used to infer migration events between those tissues. This is similar to viral phylogeography, which uses evolutionary trees built from DNA sequences to understand the spread of viruses. An analogous framework could be used to track B cells as they migrate between tissues and differentiate into cellular subtypes. To show this is possible, we recently developed the first generalized methods to infer B cell migration and differentiation from sequencing data, published in PLoS Computational Biology.
In this paper, we introduce the “SP” test, which uses summary statistics to infer if migration/differentiation occurred in a particular direction along a B cell lineage tree. We’ve already used this test in collaborations to identify the origins of pathogenic B cells in the autoimmune disease myasthenia gravis, to understand the role of atypical memory B cells in HIV infection, and to track the spread of cells between the nose and lungs in asthma (Ohm-Laursen et al., 2021). The SP test performs well in simple test cases, but it is also approximate and not appropriate in many cases. One major future project will be to develop these summary statistic-based approaches into full statistical models that will be even more useful.