Specific expression of activation-induced cytidine deaminase (AID), a novel member of the RNA-editing deaminase family in germinal center B cells

We have identified a novel gene referred to as activation-induced deaminase (AID) by subtraction of cDNAs derived from switch-induced and uninduced mu rine B lymphoma CH12F3-2 cells, more than 80% of which switch exclusively t o IgA upon stimulation. The amino acid sequence encoded by ALD cDNA is homo logous to that of apolipoprotein B (apoB) mRNA-editing enzyme, catalytic po lypeptide 1 (APOBEC-1), a type of cytidine deaminase that constitutes a cat alytic subunit for the apoB mRNA-editing complex. In vitro experiments usin g a glutathione S-transferase AID fusion protein revealed significant cytid ine deaminase activity that is blocked by tetrahydrouridine and by zinc che lation. However, AID alone did neither demonstrate activity in C to U editi ng of apoB mRNA nor bind to AU-rich RNA targets, AID mRNA expression is ind uced in splenic B cells that were activated in vitro or by immunizations wi th sheep red blood cells. In situ hybridization of immunized spleen section s revealed the restricted expression of AID mRNA in developing germinal cen ters in which modulation of immunoglobulin gene information through somatic hypermutation and class switch recombination takes place. Taken together, these findings suggest that AID is a new member of the RNA-editing deaminas e family and may play a role in genetic events in the germinal center B cel l.