BCR signaling

The B cell receptor (BCR) and its downstream signaling pathways are attractive therapeutic targets because the vast majority of B cell lymphomas express the receptor. In B cell physiology the BCR is not only essential for antigen recognition but also for the survival of mature B cells and most malignant B cells. Recent studies demonstrated that survival signals mediated by the BCR are replaced by constitutive PI3K signaling in mature B cells. Although new inhibitors efficiently targeting BCR mediated signaling are available, the signaling cascade and its regulators are still elusive in normal and malignant B cells. To identify details of the signaling cascade, we will combine genetic ablation of the BCR in mature B cells with the genetic activation of candidate genes in an in vivo approach (Srinivasan et al., Cell 2009).