Researchers from the Wellcome Sanger Institute have developed a computational pipeline for mapping immune cell development. The tool, described in a recent paper published in Nature Biotechnology, facilitates better understanding of the origins of immune cells and the impacts of disease.
B cells and T cells are crucial components of the adaptive immune system, recognising and killing specific pathogens and other dangers to the host, such as cancerous cells. The development of B and T cells involves a process known as V(D)J recombination, in which variable, diversity and joining gene segments are randomly selected through a ‘cut and paste’ process to create unique immune receptors. This results in a large amount of genetic diversity within B and T cell populations (Figure 1).
Figure 1. Diagram showing the creation of a unique antigen receptor. D (diversity) and J (joining) segments are first chosen and are ‘stuck’ together before a V (variable) segment is added. Taken from Roth, 2014.
The development of these cells is a well-studied process, but the full potential of single cell technologies combined with immune receptor sequencing has not yet been harnessed. In an effort to address this, and obtain a full picture of immune cell development, the team from the Wellcome Sanger Institute developed Dandelion, part of the Human Cell Atlas Initiative.
So-called for the immune cells’ similarities to dandelion seeds, Dandelion was created using a combination of single cell RNA sequencing and adaptive immune receptor sequencing (scVDJ-seq) data. By assessing this data, more can be learned about the origins of the immune cells, and Dandelion improves upon previous techniques for trajectory alignment. These new insights can help to understand not only how immune cells develop, but how certain diseases impact this development. For example, some cancers can influence the production of T cells, leading to a compromised immune system.
The team from the Sanger Institute also used the tool to assess the outcomes of partial recombination – a phenomenon that occurs when V(D)J recombination is disrupted and not completed. The team discovered that this process occurs in natural killer cells – a component of the innate immune system. This implies that natural killer cells are initially on a trajectory to become T cells, yet ultimately terminate the process.
An open resource
Understanding how immune cells come to be is key to understanding how human disease can influence the immune system. Dandelion improves upon previous methods for understanding immune cell development, and as an open access resource, can be utilised by researchers worldwide to gain a clearer picture of these processes. First author Chenqu Suo stated in a press release: “We have created Dandelion as a free tool that can be used openly all around the world, giving researchers another way to further explore immune cells in detail. We hope that it will be useful to the community for exploring lymphocyte biology in the single-cell space, generating new insights that will help advance our understanding of immune cell development and function in health and disease.”
Discussing Dandelion’s place in the Human Cell Atlas Initiative, co-senior author Sarah Teichmann added: “The Human Cell Atlas aims to detail all the cells and their interactions at different stages of life, giving novel insights into every cell in the human body. Developing new tools and analysis platforms, such as Dandelion, allows us to pull out these insights from the huge amount of data that the Human Cell Atlas is generating. Dandelion is a vital and freely available tool that allows us to understand more about the immune system.”