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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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Blood, 1 May 2003, Vol. 101, No. 9, pp. 3574-3580
IMMUNOBIOLOGY
Expression of activation-induced cytidine deaminase in human
B-cell non-Hodgkin lymphomas
Jobst Greeve,
Antje Philipsen,
Kristina Krause,
Wolfram Klapper,
Klaus Heidorn,
Brian E. Castle,
Joe Janda,
Kenneth B. Marcu, and
Reza Parwaresch
From the Zentrum für Innere Medizin, Medizinische
Klinik I, Universitätsklinikum Hamburg-Eppendorf,
Germany; Klinik für Allgemeine Innere Medizin,
Inselspital, Universitätsspital Bern, Switzerland;
Institut für Hämatopathologie and Lymph Node Registry Kiel,
Christian-Albrecht-Universität Kiel, Germany;
Biology Department, Boehringer Ingelheim Pharmaceuticals, Ridgefield,
CT; and Biochemistry and Cell Biology Department, Institute for Cell
and Developmental Biology, State University of New York, Stony
Brook.
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
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 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
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
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 not 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.
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