Journal
BLOOD
Volume 101, Issue 9, Pages 3574-3580Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2002-08-2424
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Funding
- NIGMS NIH HHS [R01 GM026939-21, GM26939] Funding Source: Medline
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Activation-induced cytidine deaminase (AID) induces somatic hypermutation (SHM), class switch recombination (CSR), and immunoglobulin gene conversion in B-lymphocytes. Here we report for the first time the expression of AID in healthy human B-lymphocytes and in B-cell non-Hodgkin lymphomas (B-NHL). AID mRNA expression in humans is restricted to the CD19(+)CD38(+)IgD(-) germinal center cells, namely the CD10(+)CD38(+)CD44(-) centro-blasts. After in vitro stimulation of naive human B cells by CD40-L and IL-4, AID mRNA is strongly induced for only 48 hours. In a survey of human B-NHL-AID was found to be constitutively expressed in follicular lymphoma and in diffuse large B-cell lymphoma but to be absent in B-precursor lymphoblastic leukemia, in mantle cell lymphoma, and in plasmia cell myeloma. In B-cell chronic lymphatic leukemia, in immunocytoma, and in extra-nodal marginal zone B-cell lymphoma of MALT, AID mANA was expressed only in some samples. In follicular lymphoma and diffuse large B-cell lymphoma, the expression of AID mRNA was coincident with the presence of SHM in the variable region exons of the immunoglobulin heavy-chain gene. In human B-NHL, the AID mRNA is spliced into 4 different variants but does riot contain point, mutations. Thus AID, which is highly regulated during healthy B-cell development, is constitutively expressed in human germinal center B-NHL and in subsets of nongerminal center B-NHL. This constitutive expression of AID may promote illegitimate DNA recombinations and somatic mutations in B-NHL. (C) 2003 by The American Society of Hematology.
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