The Function of AID in Somatic Mutation and Class Switch Recombination : Upstream or Downstream of DNA Breaks

The immune system has evolved specific mechanisms to combat a potentially limitless number of foreign pathogens using a limited arsenal of Ig genes. To diversify the coding potential of the Ig genes, B cells undergo several processes of regulated genetic alterations. Early in their development, B cells in the bone marrow undergo V(D)J recombination to juxtapose variable region V, D, and J segments in different combinations, creating a large repertoire of antibodies (1). Later in B cell development, usually after antigen-dependent activation of B cells, the genetic alteration processes of somatic mutation (SM), class switch recombination (CSR), and gene conversion further diversify the antigen-recognition repertoire as well as the effector function of encoded antibodies. In SM, which is the dominant means of secondary alteration of variable region gene sequences in humans and mice, mutations are introduced in the Ig variable region genes at...