Recent studies have investigated whether particular DNA repair pathways are involved in the somatic hypermutation mechanism that increases antibody diversity. The primary mutation mechanism still functions in mice carrying knockouts of all repair genes examined, but mismatch repair defects affect the final outcome.

Hyper-immunoglobulin M (IgM) syndrome (HIGM) is a rare heterogeneous primary immune deficiency. We describe a patient with HIGM characterized by skewed production of serum IgG subclasses and normal somatic hypermutation. This case may represent a subgroup of HIGM type 4 that is characterized by a biased switching to the V-region proximal constant regions.

AID is a cytidine deaminase essential for class switch recombination and somatic hypermutation during the humoral immune response. In this issue of Immunity, Gourzi et al. (2006) show that AID also plays a critical role in innate immunity to virally induced acute pro-B cell leukemia.

Somatic hypermutation and switch recombination of immunoglobulin genes require the activity of the activation-induced deaminase, AID. Recent studies of mice deficient for the uracil-DNA glycosylase UNG, which removes U from DNA, suggest that AID catalyses the deamination of dC to dU during antibody diversification.

Somatic hypermutation is the most critical mechanism underlying the diversification of Ig genes. Although mutation occurs specifically in B cells during the germinal center reaction, it remains a matter of debate whether the mutation machinery also targets non-Ig genes. We have studied mutations in the 5' noncoding region of the Bcl6 gene in different subtypes of lymphomas. We found frequent hy...

Recent work indicates that mutations in a cytidine deaminase homologue ablate both immunoglobulin class switch recombination and somatic hypermutation. These findings now explain cases of autosomal hyper-IgM syndrome and reveal that critical components for key functions of B cells require RNA editing.