title: Gastric MALT lymphoma B cells express polyreactive, somatically mutated immunoglobulins.
abstract: Gastric B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) arises against a background of chronic inflammation caused by persistent Helicobacter pylori infection. The clinical and histopathologic features of the human tumor can be reproduced by Helicobacter infection of BALB/c mice. In this study, we have analyzed the antibody sequences and antigen specificity of a panel of murine and human MALT lymphoma-derived antibodies. We find that a majority of tumors in patients as well as experimentally infected mice are monoclonal. The tumor immunoglobulin heavy chain genes have undergone somatic hypermutation, and approximately half of all tumors show evidence of intraclonal variation and positive and/or negative selective pressure. Recombinantly expressed MALT lymphoma antibodies bind with intermediate affinity to various unrelated self- and foreign antigens, including Helicobacter sonicate, immunoglobulin G (IgG), DNA, and stomach extract; antigen binding is blocked in a dose-dependent manner in competitive enzyme-linked immunosorbent assays. A strong bias toward the use of V(H) gene segments previously linked to autoantibodies and/or polyreactive antibodies in B-cell malignancies or autoimmune pathologies supports the experimental finding of polyreactivity. Our results suggest that MALT lymphoma development may be facilitated by an array of local self- and foreign antigens, providing direct antigenic stimulation of the tumor cells via their B-cell receptor.
authors: Institute of Molecular Cancer Research, University of Zürich, Zürich, Switzerland.
authors: Vanessa J
authors: VJ
authors: Craig
authors: Isabelle
authors: I
authors: Arnold
authors: Christiane
authors: C
authors: Gerke
authors: Minh Q
authors: MQ
authors: Huynh
authors: Thomas
authors: T
authors: Wündisch
authors: Andreas
authors: A
authors: Neubauer
authors: Christoph
authors: C
authors: Renner
authors: Stanley
authors: S
authors: Falkow
authors: Anne
authors: A
authors: Müller
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D004252:DNA Mutational Analysis; D005260:Female; D005753:Gastric Mucosa / Q000276:immunology* / Q000473:pathology; D016481:Helicobacter Infections / Q000150:complications / Q000235:genetics / Q000276:immunology; D016480:Helicobacter pylori; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D018442:Lymphoma, B-Cell, Marginal Zone / Q000209:etiology / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation / Q000502:physiology; D027041:Somatic Hypermutation, Immunoglobulin / Q000502:physiology
chemical_list: D007136:Immunoglobulins