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Prepublished online as a Blood First Edition Paper on January 2, 2003; DOI 10.1182/blood-2002-08-2424.

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2002-08-2424v1
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Submitted August 9, 2002
Accepted December 23, 2002

Expression of activation-induced cytidine deaminase in human B-cell non-Hodgkin's lymphomas

Jobst Greeve*, Antje Philipsen, Kristina Krause, Wolfram Klapper, Klaus Heidorn, Brian E Castle, Joe Janda, Kenneth B Marcu, and Reza Parwaresch

Medizinische Klinik I, Universitaetsklinikum Hamburg-Eppendorf, Hamburg, Germany
Klinik fuer Allgemeine Innere Medizin, University Hospital Bern, Bern, Switzerland
Institut fuer Haematopathologie und Lymphknotenregister der Deutschen Gesellschaft fuer Pathologie, Christian-Albrecht-Universitaet Kiel, Kiel, Germany
Biology Department, Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT, USA
Biochemistry and Cell Biology Department, SUNY at Stoney Brook, Stony Brook, NY, USA

* Corresponding author; email: greeve{at}uke.uni-hamburg.de.

Activation-induced cytidine deaminase (AID) induces somatic hypermutations (SHM), class switch recombination (CSR) and immunoglobulin gene conversion in B-lymphocytes. Here we report for the first time the expression of AID in normal human B lymphocytes and in B cell non-Hodgkin`s lymphomas (B-NHL). AID mRNA expression in man is restricted to the CD19+CD38+IgD- germinal center cells, namely the CD19+CD38+CD44- centroblasts. After in vitro stimulation of naive human B cells by CD40-L and IL-4, AID mRNA is strongly induced for only 48 h. In a survey of human B-NHL, AID was found to be constitutively expressed in follicular lymphomas and in diffuse large B-cell lymphomas, but to be absent in B precursor lymphoblastic leukemia, in mantle cell lymphoma and in plasma cell myeloma. In B cell chronic lymphatic leukemia, in immunocytoma and in extranodal marginal zone B cell lymphoma of MALT, AID mRNA was expressed only in some samples. In follicular lymphomas and diffuse large B cell lymphomas, 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 four different variants, but does not contain point mutations. Thus, AID which is highly regulated during normal B cell development is constitutively expressed in human germinal center B-NHLs and also in subsets of non-germinal center B-NHLs. This constitutive expression of AID may promote illegitimate DNA recombinations and somatic mutations in B-NHLs.


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