Signal transduction from the antigen receptors of B and T cells

Lead Research Organisation: The Francis Crick Institute

Abstract

White blood cells are an essential part of the immune system that protects us from infections. We are studying the biochemical processes inside these white blood cells that control how these cells respond to infection. Knowledge of these processes will provide opportunities for rational therapeutics that could be used to modulate the function of these critical blood cells.

Technical Summary

This work was supported by the Francis Crick Institute which receives its core funding from the UK Medical Research Council (FC001000), the Wellcome Trust (FC001000),and Cancer Research UK (FC001000)

The development, activation, differentiation and survival of lymphocytes are controlled by signals from multiple receptors. We are using genetic, biochemical and imaging techniques to study signalling pathways in these processes. A key area of interest is the signals that control survival of naïve B cells. We showed that signals from BAFFR that are required for B cell survival are transduced via the B cell antigen receptor (BCR) to the SYK tyrosine kinase, demonstrating, unexpectedly, that BAFFR co-opts the BCR signaling pathway. We are now investigating the molecular mechanism by which BAFFR transduces signals using proteomics, transcriptomics and genetic screens. As an extension of this we are exploring signalling pathways controlling survival of memory B cells. Migration and adhesion of lymphocytes are critical for development, activation and differentiation of lymphocytes and hence play an essential role in regulating the adaptive immune response. We recently used a genetic screen to discover a novel pathway controlled by the WNK1 kinase, which regulates T cell adhesion and migration. Future studies aim to understand the molecular mechanisms by which this pathway regulates these cellular processes, and the role of this pathway in immune responses.

Publications

10 25 50