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Current Immunology Reviews
ISSN (Print): 1573-3955
ISSN (Online): 1875-631X
VOLUME: 9
ISSUE: 2
DOI: 10.2174/15733955113099990007









Origins and Consequences of AID Expression in Lymphoid Neoplasms

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Author(s): Damien Montamat-Sicotte, Florencia Palacios, Javier M. Di Noia and Pablo Oppezzo
Pages 72-85 (14)
Abstract:
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.
Affiliation:
(Pablo Oppezzo) Institut Pasteur de Montevideo, Unit of Recombinant Protein, Mataojo 2020, Montevideo (11400), Uruguay.