Single-cell RNA seq technologies for immunology
B cells, which comprise a major component of the immune system, function primarily by secreting antibodies that bind and neutralize pathogens. Antibodies are produced by the paired expression of a “heavy chain” (IgH) immunoglobulin gene and a “light chain” (IgL) immunoglobulin gene. The unique combination of heavy and light chain genes defines the immunological activity of a B cell as well as its identity, also referred to as its clonotype. In order to deal with the near infinite array of pathogenic structures that may face the immune system, B cells exhibit an incredible level of diversity, mostly by recombining multiple gene segments to form functional mature antibody genes.
The advent of Next Generation Sequencing and single-cell RNA-Seq transcriptomics now make it possible to obtain the clonotype and transcript of each individual cell in a population of antigen-specific B cells. Our lab developed a computational algorithm that can accurately reconstruct the recombined antibody gene sequences in B cells. This algorithm, BALDR – “BCR Assignment of Lineage using De novo Reconstruction", allows us to identify clonotypes and combine them with gene expression data in individual cells. Ongoing research is deploying single-cell RNA-Seq and BALDR analysis in a number of clinical and pre-clinical trial studies for HIV, SIV and HCV, and for antibody cloning.
