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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-27476

Craig, V J; Arnold, I; Gerke, C; Huynh, M Q; Wundisch, T; Neubauer, A; Renner, C; Falkow, S; Mueller, A (2010). Gastric MALT lymphoma B cells express polyreactive, somatically mutated immunoglobulins. Blood, 115(3):581-591.

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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 histopathological 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, IgG, DNA and stomach extract; antigen binding is blocked in a dose-dependent manner in competitive ELISAs. A strong bias towards the use of V(H) gene segments previously linked to auto- 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.

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35 citations in Web of Science®
35 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Oncology
04 Faculty of Medicine > Institute of Molecular Cancer Research
07 Faculty of Science > Institute of Molecular Cancer Research

08 University Research Priority Programs > Systems Biology / Functional Genomics
DDC:570 Life sciences; biology
610 Medicine & health
Language:English
Date:17 November 2010
Deposited On:15 Jan 2010 08:14
Last Modified:27 Nov 2013 22:20
Publisher:American Society of Hematology
ISSN:0006-4971
Additional Information:This research was originally published in Blood. Blood First Edition Paper, prepublished online November 17, 2009; DOI 10.1182/blood-2009-06-228015. Copyright by the American Society of Hematology
Publisher DOI:10.1182/blood-2009-06-228015
PubMed ID:19965661

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