Antibody diversification: mutational mechanisms and oncogenesis.

ABSTRACT

Antibody diversification processes play a major role in protecting humans from pathogens. Somatic hypermutation and gene conversion increase the affinity of pathogen-specific antibodies by changing the sequence within antibody variable genes, while the class switch recombination (CSR) process changes the antibody's effector function by replacing the constant region of the antibody gene with a different constant region. Activation-induced cytidine deaminase (AID) initiates each of these three processes by deaminating cytidines within antibody genes, while a host of other DNA transacting factors are involved in either creating new mutations or repairing DNA lesions introduced during these processes. This review will discuss the main features of antibody diversification and their role in lymphomagenesis, highlight outstanding issues and questions that remain in the field, and discuss our contributions to this field.