Origins and Consequences of AID Expression in Lymphoid Neoplasms
Damien Montamat-Sicotte, Florencia Palacios, Javier M. Di Noia and Pablo Oppezzo
Affiliation: (Pablo Oppezzo) Institut Pasteur de Montevideo, Unit of Recombinant Protein, Mataojo 2020, Montevideo (11400), Uruguay.
The enzyme Activation-induced cytidine deaminase (AID) initiates somatic hypermutation (SHM) and class
switch recombination (CSR) of the immunoglobulin (Ig) genes, which are critically important for an effective immune
response. In addition, AID seems to contribute to B cell tolerance in mice and humans by, in some still undefined way,
eliminating developing autoreactive B cells. As a trade-off for the benefits brought about by its physiological roles, AID
can also contribute to cellular transformation and tumor progression through its mutagenic activity.
AID deaminates deoxycytidines at the Ig genes thereby generating deoxyuridine, which as part of the normal mechanism
of SHM and CSR is processed by DNA repair enzymes into a larger spectrum of point mutations and also DNA doublestrand
breaks. Multiple mechanisms regulate AID function to minimize deleterious or pathogenic DNA damage during
antibody gene diversification. Despite this, off-target AID activity still makes point mutations and initiates chromosomal
translocations that affect tumor suppressor and proto-oncogenes associated with B-cell lymphoid neoplasms. Through this
collateral damage, AID is etiological for the development of lymphoma in several mouse models and is expressed in many
human malignancies of mature B-cell origin where it may contribute to tumor clonal evolution. Mounting evidences
indicate a role for AID also in disease progression and worsening of the prognosis of Chronic Lymphocytic Leukemia
(CLL) and Chronic Myelogenous Leukemia (CML). Since these leukemia are not immediately derived from germinal
center B cells, normal AID regulation might not be fully functional in those cases. This review discusses recent findings
on the role of AID in lymphomagenesis. We describe the multilevel regulation of AID expression and function in normal
compared to tumor B cells, specially focusing on the emerging role of AID in CLL and CML.
Keywords: Activation-induced cytidine deaminase, antibody diversity, lymphoid neoplasms, CLL.
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