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Blood, 15 March 2006, Vol. 107, No. 6, pp. 2470-2473.
Prepublished online as a Blood First Edition Paper on November 3, 2005; DOI 10.1182/blood-2005-06-2502.
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IMMUNOBIOLOGY
Brief report
AID expression identifies interfollicular large B cells as putative precursors of mature B-cell malignancies
Gerhard Moldenhauer,
Sergey W. Popov,
Beate Wotschke,
Silke Brüderlein,
Petra Riedl,
Nicolas Fissolo,
Reinhold Schirmbeck,
Olga Ritz,
Peter Möller, and
Frank Leithäuser
From the Department of Molecular Immunology, German Cancer Research Center, Heidelberg, Germany; and the Department of Pathology, and the Department of Medical Microbiology and Immunology, University of Ulm, Ulm, Germany.
Neoplastic transformation of mature B cells can be triggered by class-switch recombination of the immunoglobulin gene, which aberrantly targets a protooncogene and promotes translocation. Class-switch recombination is initiated by the B-cell-specific protein activation-induced cytidine deaminase (AID). Using immunohistochemistry with a newly generated monoclonal antibody and quantitative reverse-transcription-polymerase chain reaction (RT-PCR) on microdissected tissue from lymph node, tonsil, and thymus, we demonstrate that AID expression is found in secondary lymphoid organs outside germinal centers and in the thymic medulla at substantial levels. This is accompanied by the presence of circle transcripts, indicating class-switch recombination to be active at these sites. The dominant AID-expressing cell population outside germinal centers displays cytomorphologic properties corresponding to those that define the recently characterized interfollicular large B-cell subset. These findings indicate that interfollicular large B cells and AID-expressing B lymphocytes of the thymic medulla could give rise to mature B-cell malignancies. (Blood. 2006;107:2470-2473)
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