How are different B cell populations developmentally linked in human health?

Project Overview

Immunological health relies on a balance between the ability to mount an immune response against potential pathogens and tolerance to self. B and T cells are key to the immune response by producing antibodies and cytotoxic T cells. B/T cell clones selectively expand following antigen recognition by B and T cell receptors (BCR and TCR) respectively.BCRs are the membrane-form of antibodies and are generated through DNA recombination resulting in the potential to recognise a vast array of pathogens. Defects in the ability to mount effective B cell or T cell responses have been implicated in infectious susceptibility, impaired surveillance of cancer and immunodeficiencies, whereas a breakdown of immunological tolerance has been attributed to autoimmune diseases such as through autoantibody production and reduced numbers of regulatory B/T cells.

This project will apply single-cell genetic technologies to determine the development, regulation and function of B and T cell populations in health and immunological diseases. Due to the distinct genetic sequence encoding for each B cell receptor per B cell clone, these can act as both a clonal barcode and, during somatic hypermutation, as a pseudo-molecular clock. Through the coupling of single-cell transcriptomics and B cell tracking through the B cell receptor, this project will aim to determine how different lymphocyte subsets are developmentally linked and differences in function, and therefore providing a platform to understand how B cell fate may be different in human disease. This will lead us to an understanding of why certain individuals are at greater risk of developing immunological disease, as well as to identify potential therapeutic targets or improved clinical management.

Training Opportunities

The DPhil will gain experience and training in laboratory molecular biology and single cell methods, bioinformatics and immunology. These include:

Theme

Immunology & Infectious Disease and Genetics & Genomics

Admissions

Project reference number: 981

Funding and admissions information

Supervisors

Name Department Institution Country Email
Rachael Bashford-Rogers Wellcome Trust Centre for Human Genetics Oxford University, Henry Wellcome Building of Genomic Medicine GBR rb520@cam.ac.uk
Professor John A Todd FRS FMedSci Wellcome Trust Centre for Human Genetics Oxford University, Henry Wellcome Building of Genomic Medicine GBR john.todd@well.ox.ac.uk

There are no publications listed for this DPhil project.