The delicate balance between DNA damage and repair in B cells

B cells generate a vast repertoire of B-cell receptors (BCR), which are generated by immunoglobulin (Ig) gene diversification processes. Ig diversification is initiated in the bone marrow, through the process of Variable (V), Diversity (D) and Joining (J) gene segment recombination (VDJ recombination), which is an antigen-independent and highly ordered process that requires the recombination activating gene products 1 & 2 (RAG1/2). Upon encountering antigen in secondary lymphoid organs, B cells undergo additional Ig diversifications during two processes termed somatic hypermutation (SHM) and class switch recombination (CSR), which require activation-induced cytidine deaminase (AID). Since the enzymatic activity of both the RAG1/2 complex and AID results in DNA damage, the regulation of these enzymes is crucial to ensure genomic integrity. The mechanistic aspects of this regulation are the central topics of this thesis. The results of our findings are presented in 7 chapters of this thesis.