Mechanisms of antibody gene diversification

Activation-Induced Deaminase (AID) is essential for antibody gene diversification by the distinct processes of class switch recombination, somatic hypermutation and, in some species, immunoglobulin gene conversion. Most evidence to date indicates that this is achieved through the direct deamination of cytosine residues to uracil in the DNA. Processing of this lesion is thought to trigger these processes. However, the mechanisms that direct AID to the antibody locus remain unclear. Like its homolog Apolipoprotein B editing catalytic polypeptide 1 (APOBEC1), which edits a specific mRNA cytosine, some additional proteins are likely to be required for proper targeting of the deaminase to its substrate.

My goal is to identify AID-interacting proteins and test their role in AID-dependent immunoglobulin gene conversion in the model DT40 cell culture system.