Influence of antigen on the development of MALT lymphoma.
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 H pylori links tumor cell proliferation to antigen-induced inflammation and the need for antigenic contact. Furthermore, the tumor cells correspond to antigen-activated memory B cells. To investigate the reactivity of the tumor immunoglobulins we employed in vitro-generated antibodies identical to those produced by MALT lymphoma cells. The immunoglobulin rearrangements of 7 MALT lymphomas were amplified, cloned, and expressed as single-chain fragment variable (scFv) antibodies. Antigen specificity of these 7 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 brains (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 9 peptides as binding partners of an additional 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.
Lenze
Dido
D
Institute of Pathology, Campus Benjamin Franklin, Charité-Universitätsmedizin Berlin, Germany.
Berg
Erika
E
Volkmer-Engert
Rudolf
R
Weiser
Armin A
AA
Greiner
Axel
A
Knörr-Wittmann
Constanze
C
Anagnostopoulos
Ioannis
I
Stein
Harald
H
Hummel
Michael
M
D000906:Antibodies / Q000235:genetics / Q000276:immunology*; D000912:Antibodies, Neoplasm; D000918:Antibody Specificity / Q000235:genetics / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D001923:Brain Chemistry / Q000276:immunology; D049109:Cell Proliferation; D016481:Helicobacter Infections / Q000150:complications / Q000276:immunology; D016480:Helicobacter pylori; D006801:Humans; D007150:Immunohistochemistry; D018442:Lymphoma, B-Cell, Marginal Zone / Q000209:etiology / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D009363:Neoplasm Proteins / Q000235:genetics / Q000276:immunology*; D014066:Palatine Tonsil / Q000276:immunology / Q000473:pathology; D019151:Peptide Library; D027041:Somatic Hypermutation, Immunoglobulin / Q000235:genetics / Q000276:immunology*; D044763:Ubiquitin-Conjugating Enzymes / Q000235:genetics / Q000276:immunology
D000906:Antibodies; D000912:Antibodies, Neoplasm; D009363:Neoplasm Proteins; D019151:Peptide Library; C502096:UFC1 protein, human; D044763:Ubiquitin-Conjugating Enzymes