Diversification of the immunoglobulin genes: Analysis of the molecular mechanisms in the chicken B cell line DT40.

The main goal of the work was the examination of the locus specificity of the immunoglobulin somatic hypermutation (HM) in the model system DT40. This gene diversification process is induced by the enzyme activation induced cytidine deaminase (AID). The work is of medical relevance, because non regulated activity of AID can cause mutations in the b-cell genome thereby promoting lymphoma development. Within the work an involvement of E2A transcription factors in somatic HM was verified. Beyond this, a 200 bp DNA-fragment which is part of the immunoglobulin enhancer, revealed to be both necessary and sufficient to confer the HM activity. The fragment contains a binding motif for E2A transcription factors. For the first time, a hypermutation enhancing element could be identified being small enough to make a statement on transcription factors which are involved in AID recruitment