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.
Ramiro
Almudena
A
DNA Hypermutation and Cancer Group, Spanish National Cancer Center (CNIO), Melchor Fernandez Almagro, 3, 28029 Madrid, Spain.
Reina San-Martin
Bernardo
B
McBride
Kevin
K
Jankovic
Mila
M
Barreto
Vasco
V
Nussenzweig
André
A
Nussenzweig
Michel C
MC
D000818:Animals; D000906:Antibodies / Q000235:genetics* / Q000276:immunology; D003564:Cytidine Deaminase; D006801:Humans; D017578:Immunoglobulin Class Switching / Q000235:genetics*; D016393:Lymphoma, B-Cell / Q000235:genetics*; D000090063:Proto-Oncogene Mas; D014178:Translocation, Genetic; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D000906:Antibodies; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase