“Interplay of transcription, mutation & replication in antibody maturation and genome instability in B cells”

“Antibody maturation in B cells, which involves somatic hypermutation and class switch recombination at immunoglobulin genes, is the process by which mature, high-affinity antibodies are generated in response to antigenic stimulation. At the molecular level, this involves a complex cascade of events that is initiated by transcription-coupled targeted mutagenesis and involves DNA breaks, repair and long-range chromosomal interactions. Given this genotoxic environment, B cells undergoing antibody maturation are prone to deleterious chromosomal translocations that can often be tumorigenic. Over the past few years, our group has discovered that DNA replication is a key player in both antibody maturation as well as the accompanying genome instability. My talk will cover our published and unpublished work highlighting the role of DNA replication in driving the critical cis and trans chromosomal interactions essential for antibody class switching and chromosomal translocations, respectively.“

 

Rushad Pavri

IMP, Austria