Gunilla Karlsson Hedestam Group - Research description

We work on anti-viral immune responses and immunogenetics. A central question is how immunoglobulin germline gene variation shapes the naïve B cell repertoire and how this affects functional immune responses.

Research Description

Genetic basis for B cell recognition and function

Our research focuses on the function of B lymphocytes and qualitative aspects of immunological memory. In several projects, we define anti-viral antibody responses at the clonal level by single-cell sorting memory B cells for sequence analysis of antibody V(D)J transcripts and for isolation and characterization of antigen-specific monoclonal antibodies. We also apply next generation sequencing to analyze expressed immune repertoires and to trace specific antibody lineages to understand their fate and levels of affinity maturation. Because V(D)J gene assignment is a critical first step of lineage tracing, and there is considerable genetic variation in germline V genes/alleles between subjects, we developed a computational tool that allows the generation of individualized germline V gene databases, IgDiscover. This is a major technical advance that will enable the use of individualized germline databases to become a standard element of high-quality immunological studies in both humans and experimental animals. By applying these methods, we obtain highly detailed information about polymorphisms in these genes, allowing us to investigate how the VDJ germline allele content influences the establishment of antigen-specific responses.

IgDiscover

The production of individualized genetic profiles of B cell receptor and T cell receptor V, D and J genes is central in many areas of research and for personalized medicine applications.

While standard deep sequencing approaches do not achieve necessary coverage to profile these genes, the use of IgDiscover and related technologies, can achieve this.

Recent developments of the IgDiscover pipeline include tools for high throughput genotyping and haplotype analysis.