| An important aspect of the immune response is the generation of specific antibodies. B cells can increase the affinity of their antibodies by making alterations in the immunoglobulin genes, under the pressure of antigen-driven selection. This so-called affinity maturation depends on the Activation-induced Cytidine Deaminase (AID), a DNA-mutator specifically acting on the immunoglobulin genes. It is crucial that the targeting of this enzyme is strictly regulated, as DNA mutations in other parts of the genome may be detrimental. This is exemplified by some B cell lymphomas, which presented with mutations in oncogenes brought upon by aberrantly targeted AID. Transcription is an important prerequisite for AID-targeting, but not all transcribed genes are AID's natural substrate. Therefore we try to identify the co-factors that determine the locus at which AID can exhibit its activity. Recently, a new lead into this research was established with the finding that AID-activity depends on the interaction with CTNNBL1. Although the exact function of this protein is still largely unknown, its association with factors of the RNA splicing machinery provide an intriguing link between AID targeting and transcription. This project aims to establish the role of CTNNBL1 in the targeting of AID. |
