The Role of Activation-Induced Deaminase in Antibody Diversification and Chromosome Translocations

Although B and T lymphocytes are similar in many respects including diversification of their antigen receptor genes by V(D)J recombination, 95% of all lymphomas diagnosed in the western world are of B-cell origin. Many of these are derived from mature B cells [Kuppers, R. (2005). Mechanisms of B-cell lymphoma pathogenesis. Nat. Rev. Cancer 5, 251-262] and display hallmark chromosome translocations involving immunoglobulin genes and a proto-oncogene partner whose expression becomes deregulated as a result of the translocation reaction [Kuppers, R. (2005). Mechanisms of B-cell lymphoma pathogenesis. Nat. Rev. Cancer 5, 251-262; Kuppers, R., and Dalla-Favera, R. (2001). Mechanisms of chromosomal translocations in B cell lymphomas. Oncogene 20, 5580-5594]. These translocations are essential to the etiology of B-cell neoplasms. Here we will review how the B-cell specific molecular events required for immunoglobulin class switch recombination are initiated and how they contribute to chromosome translocations in vivo.