Blood online
Home About Blood Authors Subscriptions Permission Advertising Public Access contact us
 

 
Advanced
Current Issue
First Edition
Future Articles
Archives
Submit to Blood
Search
American Society of Hematology
Meeting Abstracts
Email Alerts
 Blood, 21 January 2010, Vol. 115, No. 3, pp. 581-591.
Prepublished online as a Blood First Edition Paper on November 17, 2009; DOI 10.1182/blood-2009-06-228015.

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
blood-2009-06-228015v1
115/3/581    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Right arrow Rights and Permissions
Citing Articles
Right arrow Citing Articles via CrossRef
Google Scholar
Right arrow Articles by Craig, V. J.
Right arrow Articles by Müller, A.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Craig, V. J.
Right arrow Articles by Müller, A.
Related Collections
Right arrow Lymphoid Neoplasia
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

arrow to previous article Previous Article  |  Table of Contents  |  Next Article next article arrow

LYMPHOID NEOPLASIA

Gastric MALT lymphoma B cells express polyreactive, somatically mutated immunoglobulins

Vanessa J. Craig1, Isabelle Arnold1, Christiane Gerke2, Minh Q. Huynh3, Thomas Wündisch3, Andreas Neubauer3, Christoph Renner4, Stanley Falkow2, and Anne Müller1

1 Institute of Molecular Cancer Research, University of Zürich, Zürich, Switzerland; 2 Department of Microbiology and Immunology, Stanford University Medical School, CA; 3 Department of Hematology, Oncology and Immunology, Philipps-University, Marburg, Germany; and 4 Department of Oncology, University of Zürich, Zürich, Switzerland

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 VH 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.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?




click for free articles
home about blood authors subscriptions permissions advertising public access contact us
  Copyright © 2010 by American Society of Hematology         Online ISSN: 1528-0020