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Blood, 1 February 2006, Vol. 107, No. 3, pp. 1141-1148.
Prepublished online as a Blood First Edition Paper on October 4, 2005; DOI 10.1182/blood-2005-04-1722.


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Submitted April 28, 2005
Accepted September 23, 2005

Influence of antigen on the development of MALT-lymphoma

Dido Lenze, Erika Berg, Rudolf Volkmer-Engert, Armin A Weiser, Axel Greiner, Constanze Knorr-Wittmann, Ioannis Anagnostopoulos, Harald Stein, and Michael Hummel*

Institute of Pathology, Campus Benjamin Franklin, Charite-Universitatsmedizin Berlin, Berlin, Germany
Institute of Medical Immunology, Campus Mitte, Charite-Universitatsmedizin Berlin, Berlin, Germany
Institute of Pathology, University of Wurzburg, Wurzburg, Germany

* Corresponding author; email: michael.hummel{at}charite.de.

Mucosa Associated Lymphoid Tissue (MALT) B-cell lymphomas develop in the context of autoimmune or chronic inflammations like Helicobacter pylori induced gastritis. Remission of most gastric MALT-lymphomas after eradication of Helicobacter pylori links tumour cell proliferation to antigen-induced inflammation and the need for antigenic contact. Furthermore the tumour cells correspond to antigen-activated memory B-cells. To investigate the reactivity of the tumour immunoglobulins we employed in-vitro generated antibodies identical with those produced by MALT-lymphoma cells. The immunoglobulin rearrangements of seven MALT-lymphomas were amplified, cloned and expressed as single chain fragment variable (scFv) antibodies. Antigen specificity of these seven scFvs was analyzed by immunohistochemical staining of various normal, reactive and malignant human tissues. Also an expression library comprising approximately 30.000 proteins from human fetal brain (protein filter) and a peptide library were screened. One scFv stained a subpopulation of tonsillar plasma cells in immunohistochemical studies. On protein filters this scFv recognized the plasma cell related protein Ufc1. Peptide library screening identified nine peptides as binding partners of a further scFv. The majority of MALT-lymphoma immunoglobulins studied however showed no reactivity against antigens indicating that the tumor immunoglobulins do not play a significant role in stimulation and proliferation of the MALT-lymphoma tumor cells.


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