Immune cells images with help from the Crick's Light Microscopy STP.

Introduction

Memory B cells (Bmem) form a crucial part of immunological memory. They are long-lived and are rapidly re-activated following re-challenge with previously encountered pathogens. We are interested in how Bmem survival is regulated.

Differentiation of B cells following activation.

Figure 1: Differentiation of B cells following activation. Activation of naïve B cells by binding of antigen to the BCR, in combination with T cell help, leads to differentiation of the B cells into germinal centre B cells, memory B cells and plasma cells.

We have previously shown that the SYK tyrosine kinase is essential for the survival of Bmem. By analogy with our studies on the survival of naïve B cells, this suggests that the BCR may also be important in Bmem survival, possibly by transducing BAFFR signals (see above). Thus, we are investigating the roles of BCR and BAFFR in Bmem survival along with other potential signalling proteins.

More recently, using RNAseq we have identified a number of genes whose expression differs between Bmem and naïve B cells. We are using this to construct a novel reporter and deleter mouse strain that will permit genetic manipulations to be limited to Bmem cells. This strain will be used to investigate the roles of specific signalling molecules and transcription factors in the biology Bmem cells. Finally, we are interested in the differentiation pathways that are induced following B cell activation, leading to their differentiation into germinal centre B cells, memory B cells and plasma cells.